Background Different strategies for hepatocellular carcinoma (HCC) may have distinct effects on the immune system.The aim of this research was to investigate changes in the immunological function after transcatheter arterial chemoembolization (TACE) plus radiofrequency ablation (RFA) in HCC patients.Methods A total of 51 consecutive HCC treatment-naive patients was enrolled in this study and 20 healthy subjects served as controls.The therapeutic strategy was selected according to the tumor stage and general conditions.TACE was performed in 25 cases,TACE plus RFA in 17 and RFA in nine.All the patients underwent routine examinations and peripheral blood was harvested for the detection of lymphocyte subset by flow cytometry 1 day before,and 2 and 4 weeks after the treatment.The serum levels of alpha-fetoprotein (AFP),ALT and AST were also measured before and 4 weeks after treatment for the evaluation of therapeutic efficacy and liver function impairment.Results When compared with healthy controls,the CD4/CD8 ratio and the number of B cells and natural killer (NK) cells were significantly decreased in HCC patients before treatment (P ＜0.05).When compared with before treatment,the CD4+ cells and CD4/CD8 ratio decreased but CD8+ cells increased in the TACE group (P ＜0.05); the CD4/CD8 ratio and NK cells decreased but CD8+ cells increased in the TACE-RFA group (P ＜0.05); the CD3+ cells,CD4+ cells,CD4/CD8 ratio and NK cells increased in the RFA group (P ＜0.05).Significant differences in the CD3+ cells,CD8+ cells,CD4/CD8 ratio and NK cells were observed among groups (P ＜0.05).Moreover,the AFP level decreased and transaminase level increased in all groups (P ＜0.05).Differences of pre and post treatment between groups were statistically significant (P =0.016,0.025,0.018 respectively).Conclusions Immunity was compromised in HCC patients; TACE and TACE plus RFA lowered immunologic function to a certain extent.RFA improved it accompanied by a protective effect on liver function.