Objective: To optimize the Shenzhen universal infant hepatitis B immunization method. Methods: To analyze the long effectiveness of different immunization strategies and disease transition after hepatitis B virus infection by using cost-effectiveness method through decision-tree and Markov models among the Shenzhen newborns cohort in 2010 based on the local parameters. Results:Through the current strategies, the program of screening all pregnant women for HBsAg and vaccinating newborns of single-positive mothers combing with HBIG and vaccine would not only prevent more new cases, hepatic carcinoma and related deaths; but also gain more living years and QALYs. From the social prospect, it will save about RMB 40 million compared with the current program. Conclusion: It is suggested that Shenzhen Government should amend the current universal infant hepatitis B immunization program to gain more economic and social benefits.