BACKGROUND Prior studies suggest that sedentary behavior is a well-known risk factor for cardiometabolic diseases. However, the longitudinal association between overall siting time and kidney function decline is not known. MATERIAL AND METHODS We performed a nationwide prospective cohort study in individuals aged more than 40 years enrolled in the China Cardiometabolic Disease and Cancer Cohort (4C) study. A total of 132 123 individuals were included in this study. Sitting time was measured with the short version of the International Physical Activity Questionnaire (IPAQ). Kidney function decline was defined as an eGFR <60 mL/min/1.73 m² or more than a 30% decrease in eGFR from baseline. Multivariate Cox proportional hazards regression analyses were conducted to estimate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of the relation between kidney function decline and sitting time. RESULTS During a mean follow-up of 3.8 years, 3890 (2.9%) participants experienced kidney function decline. Longer sitting time was significantly associated with the risk of kidney function decline (aHR, 1.136; 95% CI, 1.036-1.247, P=0.007, comparing participants with baseline sitting time in the lowest quartile with those in the highest quartile) after adjustment for potential confounders. CONCLUSIONS Longer sitting time was independently and prospectively associated with a higher risk of kidney function decline. Sedentary behavior might represent a modifiable risk factor for chronic kidney disease (CKD) prevention.