Assessment of radioactive pollution of the Syrdarya river was carried out. A large number of water samples were collected over a twelve-year period from three zones: upstream of uranium mines; around uranium mines; and downstream of the mines. Samples were analyzed for gross α-, β-activity and radionuclide concentrations. Gross α-activity exceeded the permissible level in almost every water sample. Both gross α-and β-activity in Baigekum village and PV-1 mine significantly exceeded safe levels throughout entire monitoring period. Concentrations of 230 Th and 210 Pb surpassed the national intervention levels in almost all water samples. In a number of samples from Baigekum village excessive concentration of 226 Ra was observed. Furthermore, water samples collected from Tabakbulak in the spring of 2009 had extremely high levels of radionuclides. In general, elevated levels of radionuclides had been observed around the uranium mines and down the stream of Syrdarya since 2008-2009 when industrial-level production started at Zarechnoye, Khorasan and Irkol uranium deposits. The results suggest that radioactive pollution of Syrdarya in Kazakhstan is primarily caused by uranium mining activities. It is likely that the Syrdarya waters are not only unpalatable for human, but it may also not be suitable for household and agricultural use due to radioactive pollution.