Abstract: Objective To evaluate the safety and efficacy of autologous cytokine- induced killer( CIK) cells in the treatment of patients with chronic hepatitis B( CHB),and to investigate a new therapeutic strategy for CHB. Methods Peripheral blood mononuclear cells were isolated from 84 patients with CHB,and then induced to CIK cells in vitro with cytokines such as interferon- γ,interleukin- 2,and monoclonal antibody against CD3. The autologous CIK cells obtained were infused back into the individual patient. Liver function parameters,serum markers,and HBV DNA levels were evaluated before treatment and at 12,24,and 48 weeks after treatment. Fifty patients who received entecavir( ETV) treatment were used as controls. Comparison was made between HBe Ag- positive patients and HBe Ag- negative patients.Adverse reactions and kidney function were evaluated. Comparison of continuous data between the two groups was made by t test,and comparison of categorical data was made by chi- square test. Results The alanine aminotransferase( ALT) levels in both HBe Ag- positive patients and HBe Ag- negative patients in the treatment group decreased as the observation time went on. HBe Ag- positive patients in the treatment group had significant lower ALT levels than those in the control group at 12 and 24 weeks after treatment( t = 5. 03,P < 0. 01; t =4. 72,P < 0. 01). The treatment group had higher HBe Ag clearance rate and seroconversion rate than the control group at each time point.Particularly,there were significant differences in HBe Ag clearance rates at 24 and 48 weeks after treatment between the two groups( χ2=6. 85,P < 0. 05; χ2= 4. 83,P < 0. 05). Both HBe Ag- positive patients and HBe Ag- negative patients in the treatment group had higher HBV DNA levels and lower incidence rates of undetectable HBV DNA level than those in the control group. However,as the observation time went on,the HBV DNA copy level gradually decreased,and the HBV DNA clearance rate gradually increased in the treatment group. Conclusion The therapy with autologous CIK cells is safe and effective in patients with CHB during 48 weeks after treatment. In spite of a lower HBV DNA clearance rate,this therapy results in higher HBe Ag clearance rate and seroconversion rate than ETV therapy as the observation time goes on,which suggests a probably sustainable immune response after treatment with autologous CIK cells.