Objective: Intend to observe the liver injury induced by perfluorooctane sulfonic acid (PFOS) in SD rats and the protective effect of lycopene (LP) and its possible mechanism. Methods: 48 SD rats were randomly divided into 8 groups. The solvent control group of LP protection group and LP protection low, middle and high dose PFOS exposure groups were given LP suspension once a day according to their designed dose. The contents of ALT, ASP and AST in serum, the content of MDA in liver tissue and the activity of SOD and GSH-Px in liver tissue were measured after 2 months. Results: The levels of serum ALT, AST and serum ASP enzyme activity in middle and high dose PFOS groups and high dose PFOS groups were significantly higher than those in solvent control group (P < 0 05).The levels of serum ALT, ALP and AST in middle and high dose PFOS groups protected by LP were lower than those in the same dose PFOS group (P < 0 05). The content of MDA in liver tissue of rats treated with LP was significantly lower than that of rats exposed to the same dose of PFOS (P < 0.05). The contents of GSH-Px and SOD in the liver homogenate of the low, middle and high dose PFOS groups decreased compared with the solvent control group. Conclusion: PFOS can induce liver injury in rats, and lycopene can antagonize liver injury induced by PFOS through antioxidant mechanism.