Host factors such as APOBEC3G were associated with hypermutation, which might interfere with HBV replication. The need to assess the impact of APOBEC3G polymorphisms on a hepatitis B-infected population is highlighted by a previous study. Thus, our study aimed to characterize two APOBEC3G single nucleotide polymorphisms and evaluate their association among chronic carriers of hepatitis B in Burkina Faso. Three hundred forty-five (345) individuals were recruited, including 106 HBsAg positive and 239 HBsAg negative. APOBEC3G polymorphisms rs6001417 and rs8177832 DNA genotyping were characterized by TaqMan allelic discrimination. The minor allele G of rs600417 frequency was higher among participants with chronic hepatitis B. Furthermore, rs600417 was associated with the dominant model . Multivariate analysis for chronic hepatitis B risk factors shows that the risk of chronic hepatitis B for genotype CG and GG of rs6001417 seem to be significantly reduced and are, respectively, OR = 0.25 (95% CI 0.09–0.72, ) and OR = 0.08 (95% CI 0.02–0.31, ). In the analysis, the GG genotype of rs8177832 seems to increase the risk of chronic hepatitis B by more than six (6) times, and it was statistically significant OR = 6.41(95% CI 1.74–23.55, ). This study shows that APOBEC3G may be a susceptibility gene for chronic hepatitis B virus carriage in our context. The locus could contribute to the mediation of host native resistance to HBV infection.