The aim of this study was to generate a polygenic risk score (PRS) for type 2 diabetes (T2D) and test whether it could be used in identifying high-risk individuals for lifestyle intervention in a Chinese cohort. We genotyped 80 genetic variants among 5024 participants without non-communicable diseases at baseline in the Wuxi Non-Communicable Diseases cohort (Wuxi NCDs cohort). During the follow-up period of 14 years, 440 cases of T2D were newly diagnosed. Using Cox regression, we found that the PRS of 46 SNPs identified by the East Asians was relevant to the future T2D. Participants with a high PRS (top quintile) had a two-fold higher risk of T2D than the bottom quintile (hazard ratio: 2.06, 95% confidence interval: 1.42–2.97). Lifestyle factors were considered, including cigarette smoking, alcohol consumption, physical exercise, diet, body mass index (BMI), and waist circumference (WC). Among high-PRS individuals, the 10-year incidence of T2D slumped from 6.77% to 3.28% for participants having ideal lifestyles (4–6 healthy lifestyle factors) compared with poor lifestyles (0-2 healthy lifestyle factors). When integrating the high PRS, the 10-year T2D risk of low-clinical-risk individuals exceeded that of high-clinical-risk individuals with a low PRS (3.34% vs. 2.91%). These findings suggest that the PRS of 46 SNPs could be used in identifying high-risk individuals and improve the risk stratification defined by traditional clinical risk factors for T2D. Healthy lifestyles can reduce the risk of a high PRS, which indicates the potential utility in early screening and precise prevention.