Adoptive immune transfer plays an important role in clearance of hepatitis B virus (HBV) in chronic hepatitis B (CHB) patients. However, it is unclear whether cytokine-induced killer (CIK) cells could suppress HBV replication in CHB patients, especially if drug resistance develops. In this study, functional CIK cells were efficiently generated from 21 CHB patients and were transfused in an autologous manner. We found that CIK cells from the CHB patients displayed substantial proliferation and function. Administration of the CIK cells closely correlated with the decrease in the serum HBV load and improvement in liver function in some patients. The virological response rate in patients with baseline serum alanine aminotransferase (ALT) levels of >40 U/L was higher than that in patients with baseline serum ALT levels of < or = 40 U/L. Moreover, patients who had HBeAg loss or showed seroconversion generally had baseline serum ALT levels of >40 U/L. No serious side effects were observed. This protocol represents an alternative immune therapeutic strategy for the disease.