Nonalcoholic fatty liver disease (NAFLD) is characterized by hypertriglyceridemia, increased low-density lipoprotein cholesterol levels, and reduced high-density lipoprotein cholesterol (HDL-C) particles. Previous studies have shown that the total cholesterol to high-density lipoprotein cholesterol ratio (TC/HDL-C) was superior to other lipid metabolism biomarkers for predicting NAFLD risk and could be a new indicator of NAFLD. However, the association between TC/HDL-C and NAFLD in patients with hepatitis B virus (HBV) has not yet been determined.To investigate the association between TC/HDL-C and NAFLD in a population with chronic hepatitis B (CHB).In this study, 183 HBV-infected patients were enrolled. All participants underwent blood chemistry examinations and abdominal ultrasound. Univariate and multivariate logistic regression models, curve fitting analysis, and threshold calculation were used to assess the relationship between TC/HDL-C and NAFLD.The overall prevalence of NAFLD was 17.49% (n = 32) in the 183 CHB participants. The TC/HDL-C of non-NAFLD and NAFLD patients were 3.83 ± 0.75 and 4.44 ± 0.77, respectively (P < 0.01). Logistic regression analysis showed that TC/HDL-C was not associated with NAFLD after adjusting for other pertinent clinical variables. However, at an optimal cutoff point of 4.9, a non-linear correlation between TC/HDL-C and NAFLD was detected. The effect size of the left and right sides of the inflection point were 5.4 (95% confidence interval: 2.3-12.6, P < 0.01) and 0.5 (95% confidence interval: 0.1-2.2, P = 0.39), respectively. On the left side of the inflection point, TC/HDL-C was positively associated with NAFLD. However, no significant association was observed on the right side of the inflection point.This study demonstrated a non-linear correlation between TC/HDL-C and NAFLD in a population with CHB. TC/HDL-C was positively associated with NAFLD when TC/HDL-C was less than 4.9 but not when TC/HDL-C was more than 4.9.©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.