The aim of this study is to investigate the correlation between neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with nonalcoholic fatty liver disease (NAFLD).All subjects underwent medical check-ups, which included the measurement of basic clinical, biochemical tests and imaging tests. Univariate and multivariate logistic regression models and piece-wise linear regression were used to assess the relationship between NLR and PLR with NAFLD.All participants were divided into two groups: the Non-NAFLD group and the NAFLD group. Univariate analysis model indicated PLR was negatively correlated with NAFLD (P < 0.001) and NLR was not significantly associated with NAFLD (P > 0.05). Multiple logistic regression showed that no correlation between NLR and PLR with NAFLD after adjusting all covariates (P > 0.05). Interestingly, a nonlinear association was detected between NLR and PLR with NAFLD by piece-wise linear regression adjusting for all confounding factors. The inflection points of NLR and PLR were 1.23 and 42.29, respectively. On the left side of the inflection point (NLR < 1.23), a positive correlation was detected between NLR and NAFLD (β = 2.35, 95% CI: 1.20~4.61, P = 0.013). And PLR was found to be negatively associated with NAFLD on the right side of the inflection point (β = 0.99, 95% CI: 0.98~0.99, P < 0.001).This study demonstrated that the relationship between NLR and PLR with NAFLD was nonlinear after adjusting for potential confounding factors. The result suggested that PLR ≥ 42.29 might be a protective factor of NAFLD, while NLR < 1.23 might be a risk factor of NAFLD.Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.