BackgroundNon-alcoholic fatty liver disease (NAFLD) has become a growing public health problem worldwide. However, there is still lack of effective treatment strategies except lifestyle intervention. ObjectiveTo evaluate whether quercetin improves intrahepatic lipid content in patients with NAFLD. MethodsIn this randomized, double-blind, placebo-controlled crossover trial, 41 patients with NAFLD were randomly assigned to receive the quercetin (500 mg) or placebo capsules for 12 weeks, then switched interventions for another 12 weeks after a 4-week washout period. The primary outcome was intrahepatic lipid content evaluated by magnetic resonance imaging estimated proton density fat fraction. The secondary outcomes were liver function measurements, etc. Safety outcomes included blood routine. Results36 patients completed the trial. In ITT analyses, the quercetin intervention moderately decreased the intrahepatic lipid contents from 11.5±6.4% to 9.6±5.8%, compared with the placebo intervention (decreased by 0.1±2.6%, P=0.013 and adjusted P value is 0.028). Body weight and body mass index were mildly reduced by 1.5±2.6 kg and 0.5±0.9 kg/m2 after the quercetin intervention (P<0.05 and both adjusted P values are 0.038), while the reductions were only 0.2±1.8 kg and 0.1±0.7 kg/m2 after the placebo intervention. The intrahepatic lipid contents reductions were noticeably positively associated with the body weight losses after the quercetin and placebo interventions (r=0.557 and 0.412, P<0.001 and =0.007, respectively). Subgroup analyses found that the reduction of intrahepatic lipid contents in females (3.0±3.7%) was about twice as large as in males (1.4±2.5%) with a trend of statistically significance (P=0.113 and adjusted P value is 0.061). There were no significant differences in other secondary and safety outcomes. No adverse events associated with study intervention were found. ConclusionsTwelve weeks treatment of quercetin could reduce intrahepatic lipid contents in patients with NAFLD, possibly explained by a slightly larger body weight loss in the quercetin group. The trial is registered at www.chictr.org.cn as ChiCTR2100047904.The trial is registered at www.chictr.org.cn as ChiCTR2100047904.