Objective: To understand health literacy and associated factors of freshmen from Jiangsu Province, and to provide reference for youth health education. Methods: From 2017 October to 2018 October, a total of 15 602 college freshman were randomly selected from 20 universities in Jiangsu Province via stratified cluster sampling method. Structural questionnaires were used to investigate the status of health literacy. The χ 2 test and multivariate Logistic regression model were used to analyze the influencing factors of health literacy. Results: The health literacy level of college freshmen from Jiangsu Province was 20.2%, among which the literacy levels of knowledge, behavior and skills were 23.0%, 30.7% and 31.5% respectively. The literacy levels of the six public health issues, including safety and first aid, scientific health attitude, knowledge of prevention and treatment of infectious diseases, health information, basic health care, and prevention and treatment of chronic diseases, from high to low, were 72.8%, 58.7%, 28.5%, 28.2%, 20.3% and 15.9%, respectively. Multivariate Logistic regression analysis has showed that students from undergraduate colleges(OR=2.77, 95%CI=2.47-3.11), urban areas(OR=1.20, 95%CI=1.07-1.34), or southern Jiangsu regions(OR=1.10, 95%CI=1.00-1.22), being the only child(OR=1.13, 95%CI=1.03-1.25), higher maternal education level (OR=1.53, 95%CI=1.30-1.79), having both parents(OR=1.16, 95%CI=1.00-1.34), reported higher level of health literacy. Conclusion The three aspects and six dimensions of health literacy of college freshmen were unbalanced. Health literacy is a shared function of multiple factors including society, family, and individuals. It is essential to promote health education through more efforts on key issues, in order to effectively elevate the health literacy level of adolescent students.