Objective: To explore the association of health literacy with smoking attempt behavior among middle school students in China，and to provide ideas for health education for middle school students. Methods: Using stratified cluster sampling method, 1 066 students were selected from Zhejiang, Guangdong, Jiangxi, Sichuan and Guizhou provinces in China during June to November 2017, a questionnaire survey was conducted to collect health literacy and smoking attempt behavior. Results: The score of health literacy among middle school students was (13.49±1.87). Students who lived in eastern and rural areas, girls, guardians who were jointly supervised by their parents and grandparents, the only child, non smokers, and small amount of weekly pocket money had higher scores in health literacy（ t/F =9.81,3.10,11.12,2.65,3.50,4.47,2.64， P ＜0.05）. The prevalence of smoking attempt behavior was 5.5%. Multiple Logistic regression analyses showed that central and western China, drinking and low healthy literacy were positively correlated with smoking attempt behavior ( OR =2.75, 3.54, 21.62, 2.50, P <0.05). Conclusion Low healthy literacy can be used as a predictor of smoking attempt among middle school students, the health education should be conducted to control the smoking attempt behavior.