BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease among adults. High uric acid (UA) increases the incidence of NAFLD in the general population. However, further exploration is warranted to determine the relationship between UA levels and NAFLD in various populations. We conducted a historical cohort study to investigate the causality between UA and NAFLD across different weight categories. METHODS: A historical cohort was established from the Jidong community cohort. All participants were enrolled and followed up from July 1 RESULTS: Two thousand nine hundred eighty four participants were enrolled. 740 (24.8%) were assigned to UA Q1 group, 755 (25.3%) to UA Q2, 743 (24.9%) to UA Q3, and 746 (25.0%) to UA Q4. The global incidence of NAFLD was 26.0% (777/2984). The risk of NAFLD significantly increased with elevated UA levels in underweight and normal-weight participants (HR = 3.498, 95% CI: 2.413-5.072, P <
0.05). In multivariable analysis, UA showed a positive association with NAFLD, independent of other risk factors in underweight and normal-weight participants (UA Q2: 1.152 (0.761-1.743), UA Q3: 2.168 (1.489-3.157), UA Q4: 3.075 (2.103-4.196), P <
0.05). In the absence of other risk factors, high UA levels independently explained 17% of NAFLD risk in underweight and normal-weight participants. CONCLUSIONS: High UA levels serve as an independent risk factor for NAFLD in underweight and normal-weight individuals, highlighting the necessity of early NAFLD screening through monitoring liver function and UA levels, and personalized treatment plans for NAFLD patients with higher UA levels, which may include uric acid-lowering therapy and lifestyle modifications. However, the relationship between UA levels and NAFLD in overweight and obese individuals remains inconclusive.