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Water pollution is a threat to aquatic organisms, including fish, and is a global concern for aquatic biodiversity and ecosystem integrity. This study evaluates the effect of waterborne pollutants on Gangetic Mystus (Mystus cavasius) collected from the Surma River, Bangladesh between April 2018 to March 2019. Histomorphological studies of liver and kidney were carried out on 10 individual species collected at each of four sampling sites and one control site. Water quality parameters were also recorded at each site. We observed several histological alterations in the liver, including hemorrhage, pyknosis, necrosis, vacuolation, lipid droplet, nuclear alterations, and hepatocyte hypertrophy. In the kidney, the histopathological alterations included vacuolation, necrosis, hemorrhage, degeneration of glomerular tubule, dilation of Bowman's space and blood congestion. Temperature fluctuated between 19.7 ± 1.57 °C and 32.3 ± 1.74 °C, dissolved oxygen at the surface ranged from 4.15 ± 0.31 to 5.15 ± 0.35 ppm, pH ranged from 7.42 ± 0.33 to 6.50 ± 0.12, nitrite ranged from 0.022 ± 0.21 to 0.817 ± 0.02 mg/l, ammonia ranged from 0.70 ± 0.11 to 0.16 ± 0.19 mg/l and alkalinity ranged from 109.41 ± 0.02 to 14.32 ± 0.20 mg/l during the time frame of the study. Water quality parameters could not found the suitable range from November to February. The main aim of the present investigation revealed that histopathological changes of liver and kidney of Gangetic Mystus appeared to be a useful biomarker to assess the impact of toxicity of water pollution.