Different operation modes of cascade hydropower stations may have different effects on the hydrological regimes of a river. In order to quantitatively analyze the influence of different operation modes of the cascade hydropower stations on the hydrological regimes in Lhasa River, the indicators of hydrologic alteration-range of variability approach (IHA-RVA) was applied to analyze the changing degrees of Pangduo,Tangjia and Lhasa station. The results showed that the hydrological regimes of Lhasa River changed slightly under the conventional operation mode (COM), with the comprehensive changing degrees of 0.17, 0.21 and 0.20 respectively. Whereas the comprehensive changing degrees of these three stations reached 0.50, 0.54 and 0.48 respectively under the maximum-hydropower operation mode (MOM), which was classified as moderate changes. Then, the multi-series contribution rate segmentation was used to analyze the contribution rates of the variation of natural runoff, water diversion and cascade reservoir operation with different operation modes to the average monthly runoff. The contribution rates of these three factors to the change of the average monthly runoff of the Lhasa station were 0.81, 0.02 and 0.17 respectively under the COM, indicating that the dominant factor was the variation of natural runoff. The contribution rates of these three factors were 0.56, 0.06 and 0.38 respectively under the MOM, showing a significant increase in contribution rate of cascade reservoir operation. The contribution rate of the cascade reservoir operation of the MOM was 124% higher than that of the COM.