In this pilot study, we compared the dynamic changes of circulating immune cells between patients with hepatocellular carcinoma (HCC) who underwent radio frequency ablation (RFA) and hepatectomy. Seventy-three patients were enrolled in this study. Flow cytometry assay was performed to determine the immune cells in the peripheral blood mononuclear cells (PBMCs) before treatment and on days 7, 14, and 28 after treatment. We found that in the RFA group, the circulating cluster of differentiation (CD)4+ cells, the CD4+/CD8+ ratio, and natural killer (NK) cells continued to increase, and the circulating CD8+ cells continued to decrease after the treatment. In contrast, in the surgery group, the circulating CD4+ cells and CD4+/ CD8+ ratio decreased over the first seven postoperative days and then began to increase, and CD8+ cells decreased on the first 7 postoperative days and began to increase thereafter. The changes of immune cells in tumor tissues consisted of an increase in the number of CD4+ cells, CD8+ cells, CD3+ cells, and NK cells immediately after RFA. Our results show that postoperative immune function continued to improve after RFA, but after surgery, it decreased in the first week and started to improve thereafter. These findings are important for clinicians when selecting the appropriate therapy for HCC.