Metabolic dysfunction-associated steatotic liver disease (MASLD), the most common liver disease affects over 1.3 billion people globally (1). Poor diet quality is a major modifiable risk factor, with the Mediterranean diet recommended for MASLD management, partly due to its favourable polyunsaturated fatty acid (PUFA) profile, including greater omega-3 intake (2, 3). However, associations between the dietary omega-6 to omega-3 (n-6: n-3) ratio, individual PUFAs and MASLD remain underexplored. This study examined associations between dietary n-6: n-3 ratio and individual PUFAs with MASLD and whether these differed according to overall diet quality in a large U.S. adult population. Seven NHANES cycles (2005–2018) were included with adults aged ≥18 years who had reliable two-day dietary recalls and who met criteria for MASLD using the Fatty Liver Index (4). Diet quality was assessed using the Healthy Eating Index-2020 (HEI-2020) (5). Associations between PUFA intakes and MASLD were assessed using binary logistic regression. Non-linearity was assessed using restricted cubic splines. Analyses were adjusted for age, sex, ethnicity, income-to-poverty ratio, diabetes and cardiovascular disease history, physical activity, smoking, total energy intake and NHANES survey cycle. PUFAs showing significant interactions with HEI-2020 (P-interaction<0.05) were further examined after stratification by the median HEI-2020 score. In adjusted analyses, docosahexaenoic acid (DHA) was associated with lower odds of MASLD (OR 0.75, 95% CI 0.57–0.99), while significant nonlinear associations were observed for the n-6: n-3 ratio and marine-derived omega-3 (eicosapentaenoic acid [EPA], docosapentaenoic acid [DPA] and DHA). Compared with the median n-6: n-3 ratio of 9.0, a ratio of 5.7 was associated with 16% lower odds of MASLD (OR 0.84, 95% CI 0.76–0.94). Marine-derived omega-3 showed a nonlinear association (P-overall=0.001; P-nonlinearity<0.001), with odds initially increasing from the median intake of 0.06 g/day, peaking at 0.10–0.12 g/day, and subsequently declining to 14% lower odds at 0.50 g/day (OR 0.86, 95% CI 0.77–0.97). Significant interactions with HEI-2020 were observed for total omega-3, alpha-linolenic acid (ALA), EPA, total omega-6, linoleic acid (LA) and arachidonic acid (AA) (all P-interaction<0.05). When stratified by the median HEI-2020 score (53.4), total omega-6 and AA were associated with higher odds of MASLD below the median. Above the median, EPA was associated with lower odds of MASLD, while total omega-6 and LA showed U-shaped associations. For AA, the odds of MASLD increased from approximately 0.12 g/day and plateaued at 0.25 g/day. In conclusion, in this nationally representative cohort of U.S. adults, associations between dietary PUFAs and MASLD were nonlinear and varied by overall diet quality. A lower n-6: n-3 ratio and higher marine-derived omega-3 intake were associated with lower odds of MASLD. These findings reinforce the importance of overall diet quality and highlight marine-derived omega-3-rich foods as a potential dietary strategy for MASLD management.