Nonalcoholic fatty liver disease (NAFLD) is a worldwide chronic liver disease. Few studies have investigated the association between NAFLD and Lipoprotein-associated phospholipase A2 (Lp-PLA2), a unique enzyme correlated with oxidative stress. The aim of this study was to assess the relationship between Lp-PLA2 and NAFLD in a Chinese community-based cohort. A total of 1587 adults aged ≥40 years were enrolled in the current study. Participants underwent a standardized evaluation. The serum Lp-PLA2 concentration was measured by ELISA and NAFLD was diagnosed by ultrasonography. Multivariable logistic regression was used to assess the association between Lp-PLA2 and NAFLD. Increased Lp-PLA2 levels were significantly associated with decreased NAFLD prevalence after adjusting for other potential confounders. The adjusted ORs of NAFLD in Q2, Q3 and Q4 compared with Q1 were 0.88 (0.64-1.21), 0.71 (0.51-0.98) and 0.67 (0.48-0.95), respectively (P < 0.05). Furthermore, the adjusted ORs of moderate and heavy NAFLD in Q2, Q3 and Q4 compared to Q1 were 0.64 (0.41-1.01), 0.48 (0.29-0.80) and 0.47 (0.28-0.79), respectively (P < 0.01). In conclusions, increased Lp-PLA2 levels were independently associated with decreased NAFLD prevalence.