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Objective To investigate the effect of perfluorooctane sulfonate （PFOS） in mice. Methods The mouse models of oxidative liver injury were established by gavage of potassium perfluorooctane at a dose of 10 mg/kg for consecutive 18 d. After model establishment, 40 mice were divided into the model control group, high-dose, medium-dose and low-dose paeoniflorin groups （100 mg/（kg·d）, 50mg/（kg·d）, 10mg/（kg·d）） and positive control group （100 mg/（kg·d）, Yiganling tablet） by random number table method, and were given with intragastric administration for consecutive 3 weeks. The serum levels of alkaline phosphatase （ALP）, aspartate aminotransferase （AST） and alanine aminotransferase （ALT）, and the levels of superoxide dismutase （SOD） and malondialdehyde （MDA） in the liver tissues of mice were determined. The histological changes of liver were observed by hematoxylin-eosin staining. Results Paeoniflorin significantly increased the SOD level, whereas decreased the MDA level in the liver tissues （both P < 0.05）, thereby effectively alleviating the oxidative liver damage caused by PFOS. Paeoniflorin could significantly reduce the serum levels of ALT, AST and ALP （all P < 0.05）, and effectively mitigated the oxidative liver damage caused by PFOS. Pathologically, paeoniflorin could effectively alleviate liver tissue congestion, local liver tissue disorder, cell and tissue edema, inflammatory cell infiltration, and local tissue necrosis induced by PFOS. PFOS could also inhibit the weight gain of mice. After paeoniflorin treatment, the inhibitory effect upon mouse weight was significantly alleviated （all P < 0.05）. Conclusions PFOS can provoke oxidative stress responses to the liver, and lead to oxidative liver injury to certain extent. Paeoniflorin exerts certain protective effect on the development of oxidative liver injury caused by PFOS.