The hydro-photovoltaic complementary operation of the cascade power stations can improve the photovoltaic (PV) consumption capacity and the total system power generation, but it also requires the cascade power stations to adjust their operation rules, which will in turn exacerbate the changes in hydrological regimes in the downstream of the cascade power stations. In order to quantitatively evaluate the impact of the hydro-photovoltaic complementary operation on the hydrological regime, an optimal model of hydro-photovoltaic complementary operation of the cascade power stations in the Lhasa River Basin was constructed based on the target of maximizing the total power generation and total guaranteed output of the power system. Then the optimal operation plans of the cascade power stations were proposed based on the model, and the degree of change in the hydrological regime of different optimal operation plans were analyzed and evaluated. The results show that the hydro-photovoltaic complementary optimal operation of cascade power stations can effectively improve the total power generation and total guaranteed output of the power system; the integrated degree of change in hydrological regime of the Lhasa River after the hydro-photovoltaic complementary operation is slightly greater than that before the operation and both of them are in the vicinity of the threshold of light change to moderate change. The results of the study can provide an approach and technical support for the hydro-photovoltaic complementary operation and integrated watershed management in the Lhasa River Basin.