Background: Self-medication behavior has great adverse effects on children. The aims of this study were to assess the prevalence of self-medication with antibiotics (SMA) among children aged 0-5 years and explore the related factors. Methods: A cross-sectional survey was conducted from 1 July 2019 to 31 July 2019 in Wuhan, Hubei Province (Central China). A structured questionnaire was used to collect data from 1188 parents of children aged 0-5 years on sociodemographic characteristics, SMA among children, antibiotic knowledge and health beliefs of SMA. Results: Of the 1188 participants, 14.32% had self-medicated their children with antibiotics in the past 6 months. The higher the degree of perceived threat (OR = 0.94, 95%CI: 0.89-1.00) and self-efficacy (OR = 0.94, 95%CI: 0.89-0.98), the less likely parents were to self-medicate their children. On the contrary, the higher the degree of perceived barriers, the more likely parents were to self-medicate their children with antibiotics (OR = 1.058, 95%CI: 1.01-1.11). Conclusions: Health beliefs of parents were significantly associated with SMA among children. In addition to extensive health education, the Chinese government should also improve the accessibility and quality of health services to reduce the barriers of parental behavior change.