As one of the major sexually transmitted infections (STIs), syphilis has made a strong resurgence in China at a rate faster than any other country since 1980s. Epidemic of the infection has focused on the groups most at risk, such as men who have sex with men (MSM), female sex workers (FSWs), particularly those women working in the service venues or on the streets, and migrants. In recent years, the Chinese government has increased its efforts to respond the epidemic. Specifically, the Ministry of Health’s recently launched 10-year national syphilis control and prevention plan includes the national milestone of achieving an explicit decline in the reported syphilis incidence and the elimination of congenital syphilis by 2020, indicating specific targets for percentages of target populations educated about syphilis, tested and treated for syphilis. Increasing political commitment, innovative screening technologies, and functional health systems have provide opportunities for China to develop the comprehensive intervention package consisting of “One integration of behavioural prevention, Two systems to be strengthened, and Three active screening accesses to high-risk groups to link One standardised treatment at clinic” to highlight the combination of behavioural and biomedical interventions for achieving the goals of the national plan. However, many significant challenges at programing and implementation levels, such as capacity of health system, affordability to STI care, trust between public health providers and clients, access to hidden populations, social stigma, confidentiality, and micro-environment to support delivery of intervention and care, still remain.