Occurrence characteristic of antibiotics in the surface water of Lake Sayram in Xinjiang were analyzed by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Ofloxacin and sulfamethoxazole were the main antibiotic pollutants in Lake Sayram. The highest concentrations of ofloxacin and sulfamethoxazole were 2.7×10⁴ ng/L and 1.8×10³ ng/L, respectively, followed by erythromycin (71.7 ng/L) and oxytetracycline (15.9 ng/L). Others were less than 10.0 ng/L. The antibiotic concentration of Lake Sayram, except for sulfamethoxazole and ofloxacin, were basically at a medium or low level compared with most surface water. Due to human activities and hydraulic flow or other factors, the concentration of antibiotics in summer was 2-4 orders of magnitude lower than that in spring, and the total concentration of antibiotics in aquaculture area (S1 site) was higher than that in other points. The risk assessment showed that erythromycin, ofloxacin and sulfamethoxazole had a high risk to the ecological environment of the lake in spring(RQ>1).