Objective To explore the relationship between CD40⁃ rs1883832 and CD40⁃ rs4810485 gene polymorphisms and the genetic susceptibility and prognosis of hepatitis B cirrhosis. Methods 480 patients with hepatitis B cirrhosis，480 patients with hepatitis B virus and 480 healthy medical examiners admitted to our hospital from February 2015 to January 2018 were selected as case group，hepatitis B group and healthy group，respectively. The polymorphisms of CD40⁃rs1883832 and CD40⁃rs4810485 were analyzed by polymerase chain reaction⁃restric⁃ tion fragment length polymorphism（PCR⁃RFLP）method，and the genotype distribution and allele frequency of the two loci were compared of the 3 groups. Follow⁃up the 2⁃year survival of the patients in the case group，the Cox regression analysis method was used to analyze the effect of CD40⁃rs1883832 and CD40⁃rs4810485 gene polymor⁃ phisms on the prognosis of patients with hepatitis B cirrhosis. The Kaplan⁃Meier method was used to analyze the survival of two patients with different genotypes，and log⁃rank test was performed. Results The frequency of CD40⁃ rs1883832 T allele in the case group was higher than that in the healthy group and hepatitis B group，and the hepa⁃ titis B group was higher than the healthy group（P < 0.05）. There was no significant difference in the frequency of CD40⁃ rs4810485 G allele between the 3 groups（P > 0.05）. Cox regression analysis showed that the CT and TT genotypes of CD40⁃rs1883832 were independent risk factors affecting the prognosis of hepatitis B cirrhosis（HR = 1.682，2.588，P < 0.05）with the prognosis of hepatitis B cirrhosis（P > 0.05）. The two⁃year mortality rate of 480 patients with hepatitis B cirrhosis was 16.55%（72/145）. Among them，thirty ⁃three patients with CD40⁃ rs1883832 gene carrying C allele （CC + CT）died，and patients without C allele（TT）died 39 cases. According to Kaplan⁃Meier survival curve anal⁃ ysis，the difference between the 2⁃year survival curves of patients with CC + CT genotype and TT genotype was statistically significant（P < 0.05）. Fifty⁃one patients with CD40⁃rs4810485 gene carrying C allele（CC+CG）died， and patients without C allele（GG）died 21 cases.. According to Kaplan⁃Meier survival curve analysis，there was no statistically significant difference between the CC + CG genotype patient and the GG genotype patient 2⁃year survival curve（P > 0.05）. Conclusion The CD40⁃rs1883832 gene polymorphism is closely related to the genetic susceptibility and prognosis of hepatitis B cirrhosis，and compared with the CC + CT genotype，patients with TT