ObjectiveTo compare the efficacy and safety of Huaier and Sorafenib in treatment of small hepatocellular carcinoma(HCC)following radical resection. MethodsEighty-two patients with small HCC accepted radical liver resection and then taken Huaier or Sorafenib were collected retrospectively. These patients were divided into Huaier group(51 cases)and Sorafenib group(31 cases)according to the different administration drugs after operation. The baseline characteristics, tumor characteristics, survival rate, tumor recurrence rate, and side effects were compared between two groups. Results①There were no significant differences on the baseline demographic characteristics, liver function, and tumor characteristics between two groups(P > 0.05).②The overall survival rate and tumor-free survival rate had no significant differences between the Huaier group and the Sorafenib group(P=0.737, P=0.699).③The rate of recurrence or metastasis had no significant difference between the Huaier group and Sorafenib group(37.3% versus 32.3%, P=0.648). The most common site of the recurrence or metastasis was the liver and the lung followed.④There were only 5 cases suffered side effects after taking Huaier and no case needed Huaier discontinuance. However, 11 cases suffered side effects after taking Sorafenib and 3 cases needed Sorafenib discontinuance, and the rate of the side effect in the Sorafenib group was much higher than that in the Huaier group(35.5% versus 9.8%, P=0.026). ConclusionFor the small HCC who accepted radical liver resection, Huaier seems to be an effective and safe drug.