Phototherapies, including sunlight, infrared, ultraviolet, visible and laser, parts of which present high curative effect, small invasion, and negligible adverse reactions in cancer treatment. Here we aimed to explore the potential therapeutical effects of blue LED in hepatoma cell and decipher the underlying cellular/molecular mechanisms. We demonstrated that the irradiation of blue LED light in hepatoma cell could lead to cell proliferation reduction along with the cell apoptosis increase. Simultaneously, blue LED irradiation also markedly suppressed the migration and invasion ability of hepatoma cells. Sphere formation analysis further revealed the decreased stemness of hepatoma cell under the treatment of blue LED irradiation. In addition, blue LED irradiation significantly promoted the expression of γ-H2AX, a sensitive molecular marker of DNA damage. Collectively, we demonstrated that blue LED irradiation exhibited anti-tumor effects on liver cancer by inducing DNA damage, representing a potential approach for human hepatoma treatment.