Abstract Background LIN28B is involved in multiple cellular developmental processes, tissue inflammatory response and tumourigenesis. The association of LIN28B polymorphisms with hepatitis B virus (HBV) infection remains unknown. Methods This study investigated the association of LIN28B rs314277, rs314280, rs369065 and rs7759938 polymorphisms in patients with chronic HBV infection, a major cause of liver disease including hepatocellular carcinoma (HCC). A total of 781 individuals including 515 cases of chronic HBV infection (91 asymptomatic carrier status, 128 chronic hepatitis, 127 cirrhosis and 169 HCC), 97 HBV infection resolvers and 169 healthy controls were investigated. Results LIN28 rs314280 genotypes GA + AA were higher in resolver and controls than patients (P = 0.011). Patients had significantly lower rs314280 allele A than resolvers (P = 0.031, OR 0.689, 95%CI 0.491–0.969) or controls (P = 0.034, OR 0.741, 95%CI 0.561–0.978). In dominant model, patients had significantly lower rs314280 genotypes AA+GA than controls (P = 0.008, OR 0.623, 95%CI 0.439–0.884). LIN28 rs7759938 genotypes TC + CC were higher in resolvers and controls than patients (P = 0.015). Patients had significantly lower rs7759938 allele C than resolvers (P = 0.048, OR 0.708, 95%CI 0.503–0.999). In dominant model, patients had significantly lower rs7759938 genotypes TC + CC than controls (P = 0.010, OR 0.632, 95%CI 0.445–0.897). Chronic hepatitis patients had lower frequency of rs369065 genotype TC than asymptomatic carriers, cirrhosis and HCC (P = 0.019). Conclusions These results suggest that LIN28 rs314280 and rs7759938 may be related to the susceptibility of chronic HBV infection. Further studies are warranted to examine the association of LIN28B polymorphisms with HBV-related diseases, especially HCC.