Abstract Background Ordinary screening of transfusion-transmissible infections (TTIs) among blood donors is essential for blood transfusion. Although there is several TTIs studies focus on human immunodeficiency virus, hepatitis B and C viruses, and Treponema pallidum infections in China, it is no data to illustrate any firm conclusion from Shiyan City, Central China. It aims to verify the seroprevalence of TTIs among blood donors at Shiyan. Methods A retrospective analysis of blood donors’ information was conducted for the presence of HIV, HBV, HCV and T. pallidum . Logistic regression analysis was used to demonstrate risk factors including age, gender and occupation associated with them. The variation tendency in seroprevalence of these TTIs over the study period was evaluated by Cochran-Armitage trend test. Results Of 211 639 blood donors, 2 858 (1.35 %) had serological evidence of TTIs. The seroprevalence of HIV, HBV, HCV and T. pallidum were 0.08 %, 0.51 %, 0.20 % and 0.57 %, respectively. However, the co-infection prevalence of TTIs has not been detected. The HIV seropositivity significantly increased among female donors (OR = 1.63, P