Abstract: Objective To examine the association between sedentary behavior and the risk of cardio-cerebrovascular disease (CCVD) mortality.Methods A nested case-control study was conducted based on a cohort of 8 275 adults (aged ≥ 18 years) during October 2010 to December 2014 in Jiangsu province.A total of 96 incident cases of CCVD were identified and 480 cohort members without CCVD event were matched to the cases at a ratio of 1:5.Unconditional logistic regression model was used to estimate the adjusted odds ratio (OR) and its corresponding 95%confidence interval (95%CI) of CCVD mortality.Results After adjustment for potential confounders including age,education,household income,smoking,alcohol drinking and blood pressure,a 6-hour daily sedentary behavior was associated with an increased risk of CCVD mortality (OR=5.94,95%CI:2.01-17.60).Interactive effect of sedentary behavior and smoking on the risk of CCVD mortality was observed.The respondents with daily sedentary behavior of ≥6 hours and current smoking were at a 2.46 times (95%CI=1.03-5.88) higher risk of CCVD mortality than that of those with daily sedentary behavior of <2 hours and never smoking.No interactive effect of alcohol drinking and sedentary behavior on CCVD mortality was found.Conclusion Sedentary behavior could increase the risk of cardio-cerebrovascular disease mortality independently or interactively with smoking.