Salinization of inland water bodies represents a significant and growing ecological and environmental challenge globally. This issue is particularly severe in the arid and semi-arid regions of northern China, where intensified lake salinization has led to the degradation of aquatic ecosystems and a decline in fishery resources. As a typical inland saline lake in Inner Mongolia, Daihai Lake has experienced continuous and aggravated salinization, resulting in a sharp reduction in aquatic biodiversity. Currently, only few small saline-alkaline-tolerant fish species persist, notably topmouth gudgeon (Pseudorasbora parva) . As a eurytopic small freshwater fish. This eurytopic fish survives Daihai""s extreme saline-alkaline conditions, suggesting strong adaptive tolerance. Nevertheless, the physiological and pathological response mechanisms of this species to salinity, alkalinity, and their combined stress remain poorly understood. The present study systematically conducted acute toxicity experiments to evaluate the effects of salinity, alkalinity, and their interactive stress on the topmouth gudgeon. In addition, histopathological analyses were performed to examine structural alterations in key tissues, including the gills, spleen, liver, and intestine. In this experiment, wild topmouth gudgeon were used as test subjects. After a 7-day acclimatization period, healthy individuals were selected for acute toxicity testing. The experimental design included a control group, five salinity groups (3, 6, 9, 12, and 15 g/L NaCl), six alkalinity groups (10, 20, 40, 60, 80, and 100 mmol/L NaHCO3), and six combined stress groups (3, 9 g/L NaCl ×10, 20, and 60 mmol/L NaHCO3). Employing semi-static 96-hr tests with triplicate replicates (10 fish each). Throughout the experiment, we recorded behavioral responses, mortality, and calculated LC50 and SC values. After 96 hours of exposure, surviving individuals from control group, high-salinity group (12 g/L NaCl), high-alkalinity group (100 mmol/L NaHCO3), and combined-stress groups (9 g/L NaCl + 60 mmol/L NaHCO3) were sampled. Tissue samples from the gills, spleen, liver, and intestine were collected, fixed in 4% paraformaldehyde, embedded in paraffin, sectioned, and stained with hematoxylin and eosin (H&E) for histopathological examination and comparative analysis. Results indicate P. parva exhibits salinity sensitivity (96-h LC50=8.597 g/L; SC=2.484 g/L). At 15 g/L salinity, the fish exhibited acute stress behaviors, including violently darting against tank walls and rapid swimming. As the exposure duration increased, these behaviors progressed to side-turning, accelerated opercular movement (reflecting increased respiration), and sluggish responses, accompanied by severe pathological manifestations such as darkened body coloration and abdominal hemorrhage, ultimately culminating in 100% mortality. Conversely, it demonstrated exceptional alkalinity tolerance (96-h LC50=146.278 mmol/L; SC=37.149 mmol/L), showing only 20% mortality and mild behavioral anomalies at 100 mmol/L. Combined stress exhibited synergistic toxicity, causing severe tissue damage. Histopathology revealed varying degrees of structural injury across multiple tissues. In the gills, high salinity induced swelling of filaments along with atrophy and disarray of lamellae, whereas high alkalinity triggered a significant increase in chloride cell numbers and severe epithelial cell shedding. Combined stress led to extensive lamellar detachment, vascular congestion, and compromised respiratory and osmoregulatory functions. In the spleen, high salinity caused vacuolation of lymphocytes and a reduction in melano-macrophage centers, while high alkalinity increased lymphocyte numbers and expanded the white pulp area. Combined stress resulted in immune cell dissolution and degeneration of the splenic medulla. In the liver, saline-alkaline stress induced hepatocyte vacuolation, nuclear displacement, sinusoidal dilation, and inflammatory cell infiltration, with the most severe damage observed under combined stress, potentially impairing energy metabolism and detoxification. In the intestinal mucosa, both high salinity and high alkalinity caused atrophy of mucosal folds and disorganization of epithelial cells. Although combined stress induced some adaptive morphological changes in the mucosal folds, epithelial cell shedding was still evident, suggesting impaired digestive and barrier functions. In summary, this study clarifies the physiological characteristics of topmouth gudgeon, revealing its sensitivity to salinity and high tolerance to alkalinity. It demonstrates that combined saline-alkaline stress produces synergistic toxic effects and, through histopathological evidence, elucidates the underlying mechanisms of structural damage in various organs. These findings provide a theoretical foundation and practical reference for further elucidating the saline-alkaline tolerance mechanisms in P. parva and for guiding the ecological restoration of salinized aquatic systems.