Abstract: Objective To elucidate the role of NEU1 siRNA on proliferation, apoptosis, and invasion of OVCAR3 cells. Methods The OVCAR3 cells were transfected with siRNA that knockdown of NEU1. The transfect dye solution preparation for control is about 250 μl Opti-mem serum-free medium, and MOCK group or interfere group were to add 5 μl MOCK siRNA (100 pmol) or NEU1 siRNA (100 pmol) to 245 μl Opti-mem serum-free medium. After 48 h, the transfected cells were collected and processed for Western blot, proliferation, cell cycle, apoptosis, and invasion assay. Results Cell viability assay and flow cytometry showed that NEU1 siRNA effectively inhibited the cancer proliferation, arrested cells cycle at G₀/G₁ phase, and induced apoptosis when compared to the Mock group. Transwell assay showed that invasion of cells in OVCAR3 treated with NEU1 siRNA were suppressed significantly. In addition, Western blot revealed that expressions of Cln3 and Cln5 were depressed, and ATP5B and ATP5J expressions were also reduced. Conclusion NEU1 siRNA can effectively inhibit proliferation, apoptosis, and invasion of human ovarian cancer cells by targeting lysosome and oxidative phosphorylation signaling, which can serve as a new target ovarian cancer treatment.