Background The co-infection of Human Immunodeficiency Virus (HIV) and syphilis is risky for pregnant women and their expected children. In 2015, the Integrated Prevention of Mother-to-Child Transmission (iPMTCT) programwas established to offer all pregnant women with free screening, counseling, and testing of HIV and syphilis during regular obstetric inspections. To summarize the phase progress of this program, we reported the trends of maternal HIV-syphilis co-infection in China. We tried to socioeconomic factors associated with HIV-syphilis co-infection to inform the stratified control strategy for future work. Methods We obtained the prevalence data of HIV and syphilis over 2011–2018 by reviewing the Sexually Transmitted Infection (STI) monthly update reporting to the central surveillance system. With health status, background characteristics, and health outcomes reported, we collected the case reports from 2,578 HIV-positive pregnant women who accepted the screening at the local clinic. The trends of HIV and syphilis prevalence were examined using the Cochran-Armitage trend test. Logistic regression was applied to detect the features associated with syphilis infection among HIV-positive women and the potential risk factor to neonatal death. Results The prevalence of HIV decreased from 0.076–0.039% among registered pregnant women but increased slightly to 0.054% in 2018. The trend of syphilis prevalence in HIV-infected pregnant women fluctuated slightly around an average of 1.80% (p = .378). Multivariate logistic regression indicated finishing education of junior high school or below (aOR: 1.79, 95%CI: 1.31–2.43; p