Background: Recent research has shown the host innate immunity plays important roles in controlling HBV infection, and interleukin-6 (IL-6) is the key factor involved in the innate immune response. It is well known that the polymorphisms of IL-6 promoter can affect both the transcription and production of IL-6. This study aims to investigate whether there is an association between the IL-6 promoter functional polymorphisms and spontaneous clearance of HBV. Methods: Two polymorphisms of the IL-6 gene, -572 C/G (rs1800796) and -597 G/A (rs1800797), were analyzed by DNA sequencing in a case control study including 219 cases with chronic HBV infection and 212 controls spontaneously recovered from HBV infection. Results: For IL-6 -572 C/G, the controls with spontaneous clearance of HBV have significantly higher allele G (0.302 vs. 0.21, p = 0.002) and GG genotype frequency (0.075 vs. 0.032, p = 0.006) compared to the chronic HBV infection patients. The odds ratio (OR) for the G allele was 0.61 (95% confidence interval ICI]: 0.45 - 0.84). For 597 G/A, all subjects are GG genotype except one GA genotype in the recovered controls, no significant differences in allele or genotype frequencies between the case group and control group were observed. Conclusions: These findings indicate that the IL-6 -572 allele G may be beneficial for spontaneous clearance of HBV.