Previous studies on Chinese showed mixed results describing the relationship between obesity and mortality. The optimum levels of body mass index (BMI) and waist circumference (WC) are inconsistent. In the Guangzhou Biobank Cohort Study, after excluding ever smokers and those with poor health, 19,405 Chinese (50+ years) recruited from 2003 to 2008 were followed-up until 2017. During an average follow-up of 11.5 (standard deviation = 2.3) years, 1,757 deaths were recorded. All-cause mortality showed a J-shaped association with BMI, with the lowest mortality risks at 22.5 kg/m2 for both men and women. In those with BMI ≥ 22.5 kg/m2, an increase of 5 kg/m2 was associated with 29% higher all-cause mortality (hazard ratio (HR) = 1.29, 95% confidence interval (CI) 1.15-1.46), 30% higher cancer mortality (1.30, 95% CI 1.08-1.57), and 37% higher cardiovascular disease (CVD) mortality (1.37, 95% CI 1.13-1.67) after adjustment for potential confounders. In this first cohort study in one of the most economically developed cities in China, the lowest all-cause mortality was observed for a BMI of 22.5 kg/m2 in all participants, and a WC of 78 cm in men and 72 cm in women.