Objective: To study the current status and influencing factors of health literacy and physical health of 1 215 high school students in urban and rural region of Jiangsu province. Methods: Multi-stage sampling method (stratified sampling and random sampling) was used in this study. 1 284 questionnaires were distributed and returned from 8 schools in urban and rural region of Jiangsu province, 1 215 of which were effective, representing a response rate of 94.62 % (1 215/1 284). Using independent-samples t-test, one way ANOVA analysis, and multiple linear regression model to analyze the correlation between family economic factors and health literacy or total score of physical health, and to establish the model equation. Results: The rate of students with health literacy was 8.45 %. The passing rate of physical fitness test was 67.56 %, with the good rate of 27.25 % and the excellent rate of 1.1 %. The health literacy score of urban high school students was higher than that of township. The total score of health literacy of students from the key high schools was higher than that of the normal high schools. Except for the pull-up score (P＜0.05), there was no statistical significance in the comparison of physical fitness test score of high school students with different educational background of their father, with the comparison of basic knowledge scores (P＜0.05) and the total health literacy test scores (P＞0.05). There was no significant difference in the physical fitness test scores of high school students with different educational background of their mother, except for the sit-ups scores of girls (P＜0.05). There was statistically significant difference in the comparison of total score of health literacy test and the scores of basic knowledge and lifestyle (P＜0.05).The total score of the physical fitness test of high school students with an annual family income of 50 000-79 900 CNY was the highest, the comprehensive level of the health literacy test of high school students with an annual family income of 80 000-99 900 CNY was the highest, and the high school students with annual family income of less than 10 000 CNY had the lowest scores. The results indicated that here was a positive correlation between the total score of physical fitness test and the skill practice test score, school location and father's education. Conclusion: The physical health level of high school students in urban and rural areas of Jiangsu province is good, but the health literacy is low. There is a positive correlation between the total score of physical fitness test and the skill practice test score, school location and father's education. The mothers' education background and high-level family annual income of high school students affect their physical health and health literacy mostly.