The aim of this study is to assess the HIV/syphilis epidemic among men who have sex with men (MSM) aged <50 years and ≥50 years in Shenzhen, and explore the associated factors of HIV/syphilis co-infections among MSM in Shenzhen, in order to help prevention and intervention programs determine their target sub-group. A serial cross-sectional study was conducted on MSM in Shenzhen city, China from 2009 to 2017. A questionnaire was used to collect demographic characteristics, history of HIV testing, history of blood donation and sexual behaviors. 5 ml of venous blood were collected for syphilis and HIV tests. The overall prevalence of HIV, syphilis, HIV/syphilis co-infection was 9.40%, 18.97%, and 4.91%, respectively. The prevalence of HIV (15.26%), syphilis (27.71%), HIV/syphilis co-infection (9.24%) in aged ≥50 years MSM was significantly higher than aged <50 years MSM (9.15%, 18.59% and 4.72%, respectively). The following factors were found to be significantly associated with HIV/syphilis co-infections (P<0.05): age≥50 years (OR = 1.78, 95% CI = 1.10-2.87), high school or lower (OR = 1.49, 95% CI = 1.10-2.01), monthly income ≤436.2 USD (OR = 1.74, 95% CI = 1.25-2.42), monthly income 436.4-727.2 USD (OR = 1.46, 95% CI = 1.05-2.03), ≥2 anal sex partners in the past 6 months (OR = 1.59, 95% CI = 1.02-2.49), ≥2 oral sex partners in the past 6 months (OR = 1.60, 95% CI = 1.08-2.36), inconsistent condom use during anal sex in the past 6 months (OR = 1.50, 95% CI = 1.11-2.03). We found that aged <50 years and ≥50 years MSM in Shenzhen had a high prevalence of HIV/syphilis infection in a period from 2009 to 2017. Age-specific sexually transmitted diseases education, prevention, and intervention programs for aged ≥50 years MSM should be implemented urgently and integrated interventions of both HIV and syphilis infections on MSM are needed in the future.