High serum free fatty acid (FFA) levels are associated with metabolic syndrome (MS). This study aimed to assess the association of fasting serum FFAs with nonalcoholic fatty liver disease (NAFLD) in a Chinese population. A total of 840 subjects fulfilled the diagnostic criteria of NAFLD and 331 healthy control participants were enrolled in this cross-sectional study. Fasting serum FFA levels and other clinical and laboratory parameters were measured. NAFLD patients had significantly higher serum FFA levels than controls (P < 0.001). Serum FFA levels were significantly and positively correlated with parameters of MS, inflammation indexes, and markers of hepatocellular damage. Elevated serum FFA levels were found in NAFLD subjects with individual components of MS (obesity, hypertriglyceridaemia, and hyperglycaemia). Stepwise regression showed that serum FFA levels were an independent factor predicting advanced fibrosis (FIB-4 ≥ 1.3) in NAFLD patients. Serum FFA levels correlated with NAFLD and could be used as an indicator for predicting advanced fibrosis in NAFLD patients.