APOBEC3 protein families， a DNA cytidine deaminase， were up-regulated in multiple tumors. However， the relationship between Hepatocellular carcinoma (HCC) and APOBEC3B (A3B) remains unknown. It has been confirmed that interleukin-6 (IL-6) has significant impacts on oncogenesis of HCC. Here， we reported that the expression of IL-6 was substantially up-regulated by A3B in HepG2 cells. A3B induced IL-6 expression through relocating HuR to enhance the IL-6 mRNA stability. Further analysis indicated that IL-6 also increased the expression of A3B through JAK1/STAT3 signaling pathway， which formed a positive feedback to maintain the continuous expression of A3B and IL-6， and thereby promoted the prolonged non-resolving inflammation. Collectively， these findings suggest that A3B is essential for oncogenesis of HCC， and is a potential target for preventive intervention.