Multi-energy complementary power generation system linked with hydropower has become an important means to enhance clean energy consumption. The cascade hydro-photovoltaic complementary generation system is affected by the strong randomness and intermittently of photovoltaic output, which greatly limits the safe and stable operation of the complementary system. In this paper, focusing on the practical engineering problem of operation safety analysis for cascade hydro-photovoltaic complementary generation system, an operation safety analysis method of probabilistic collocation point algorithm based on polynomial chaos theory is proposed and the corresponding software is developed. The analysis method is carried out from two perspectives: one is the power generation plan safety check, and the other is the safe operation interval analysis. The application shows that the proposed analysis method can effectively deal with the solving efficiency problem brought by large-scale scene sampling with randomness, and can significantly improve the solving efficiency under the premise of ensuring calculation accuracy, which providing technical support for the safe and stable operation of the complementary system.