Abstract: Objective To evaluate the intervention strategies in Guangdong initiative for comprehensive control of syphilis (GICCS) from the aspect of health economics, and to provide the scientific basis for optimization and formulation of syphilis prevention and control strategy. Methods Two kinds of syphilis intervention strategies were considered:one was 80 percent coverage of syphilis screening (Strategy 1) and the other was 85 percent coverage of syphilis screening (Strategy 2). A Markov model for syphilis screening was applied based on the results of field surveys in GICCS and published literature. Cost-effectiveness analysis and sensitivity analysis were conducted through simulating the total costs and expected health outcomes of 10 000 syphilis high-risk people during the time horizon of 20 years under strategy 1 and Strategy 2 respectively from the societal perspective. Results Compared to strategy 1, strategy 2 would cost 3 998.88 million yuan more but avert 28 primary syphilis, 34 secondary syphilis, 337 latent syphilis and 8 tertiary syphilis cases and 392 disability adjusted life years (DALYs) at the same time. The incremental cost effectiveness ratio was 101.95 thousand yuan per DALYs. Sensitivity analyses showed that syphilis screening programme would have more cost effectiveness when the incidence of syphilis and the probability of late latent syphilis progressing to tertiary syphilis increased and the treatment rates of secondary syphilis and late latent syphilis decreased. Conclusion The syphilis intervention strategies GICCS adopts have cost effectiveness and can be popularized.