Abstract: ob＜x＞jective: To explore the related mechanisms of sulfatase-1 (SULF1) in regulating the proliferation of liver cancer cells. Methods: Western Blot and immunohistochemical experiments were used to analyze the difference of SULF1 ex＜x＞pression between normal liver tissue and primary liver cancer tissue. A stable transgenic cell line overexpressing SULF1 was constructed in HepG2 and HuH-7 cells. Edu, CCK-8, and colony formation experiments were performed to investigate the effects of SULF1 overex＜x＞pression on the proliferation of liver cancer cells. Western Blot experiments were conducted to explore the molecular mechanism of SULF1 regulating hepatoma cell proliferation. Results: SULF1 is lowly expressed in liver cancer tissues; overex＜x＞pression of SULF1 inhibits the proliferation of liver cancer cells; SULF1 can promote the ex＜x＞pression of p53. Conclusion: SULF1 acts as a tumor suppressor gene in liver cancer and inhibits the proliferation of liver cancer cells by positively regulating p53.