【Objective】 In an effort to prevent transfusion-transmitted hepatitis B infection, universal HBsAg screening, HBsAg+ MP nucleic acid test(NAT) for HBV and HBsAg + individual(ID) NAT were analyzed for cost-effectiveness. 【Methods】 On the basis of screening data and the documented parameter, the number of window period infections, chronic infections and occult infections was constructed, and cost-benefit analysis was conducted. 【Results】 Of 132 208 donations, the yield rate of ID NAT for HBsAg-/DNA+ (0.11%) was significantly higher than HBsAg+ MP NAT(0.058%). Furthermore, the predicted preventing transfusion transmitted HBV cases by ID NAT is 1.25 times as that by MP-6 NAT, so did the benefits. The cost-benefit of the three screening models were 1∶63.6、1∶28.6 and 1∶53.4. 【Conclusion】 Universal HBsAg in combination with ID HBV NAT screening was the most effective among all screening strategy. It is necessary to applied HBsAg and ID HBV NAT screening for the safety of blood transfusion.