Background Tobacco smoke and alcohol use were associated with several diseases, study on joint effect of smoke and drink was rare.Objective This study aims to investigate the joint effect of tobacco smoke and alcohol use on all-cause mortality and premature death in a contemporary cohort.Methods China Health and Retirement Longitudinal Study (CHARLS) was an ongoing nationally representative survey for subjects aged over 45 years in China, which performed every 2 years for total of 3 waves from 2011 to 2015 in China. We used weighted logistic regression model to estimate the joint effect of tobacco smoke and alcohol use on total mortality and premature death.Results After adjusting for the confounders, the odd ratios (ORs) value of all-cause mortality were 1.47 (95%CI: 1.03–2.08) and 1.51 (95%CI: 1.09–2.10) in smoker and non-drinker and smoker and drinker separately. Compared with non-smoker and non-drinker, smoker and drinker increased the odds of premature death by 3.14 (95%CI: 1.56–6.34). In the subgroup analysis, there was a 5-fold (OR = 4.95; 95%CI: 2.00-12.27) increase in the odds of premature death for female smoker and drinker.Conclusion This study found a joint effect of tobacco smoke and alcohol use on all-cause mortality and premature death among a contemporary and nationally representative data in China. Our results suggested the joint effect was more pronounced in women, but further research was needed.