Recent study showed periostin play a pivotal role in abnormal liver triglyceride (TG) accumulation and in the development of obesity-related liver fat accumulation. However, little is known regarding whether periostin plays a key role in the heightened prevalence of NAFLD and other metabolic phenotypes among large-scale populations. A cross-sectional sample of 8850 subjects aged 40 yr or older from China were evaluated in this study. Serum periostin was measured by ELISA methods. The diagnosis of NAFLD by liver ultrasonic examination. Among overweight and obese subjects, NAFLD subjects had higher serum periostin levels than those without NAFLD (126.75 ng/ml vs. 75.96 ng/ml, p < 0.001). Periostin was associated with a higher risk for NAFLD (OR 1.75 for each SD increase in periostin, 95% CI 1.04-3.37, p < 0.001) among overweight and obese subjects after confounder adjustment. Furthermore, periostin levels among overweight and obese subjects were correlated with aspartate aminotransferase (r = 0.102, p = 0.004), alanine aminotransferase (r = 0.108, p = 0.003), waist circumference (r = 0.111, p = 0.002), homeostasis model assessment index-insulin resistance (r = 0.154, p < 0.001) and fasting plasma insulin (r = 0.098, p = 0.006), TG (r = 0.117, p = 0.001). Elevated circulating periostin level was associated with an increased risk of having NAFLD and insulin resistance among overweight and obese individuals.