Abstract Insulin resistance and thyroid dysfunction are established but usually separately studied contributors to hepatic fibrogenesis in metabolic dysfunction-associated steatotic liver disease (MASLD). In a cross-sectional cohort of 188 patients with MASLD, 12 patients meeting criteria for euthyroid sick syndrome were excluded, and thyroid status was classified in the remaining 176 patients based on TSH and free T4. In a logistic regression model comparing euthyroid (n = 60) and truly hypothyroid (subclinical plus overt, n = 51) patients, adjusted for age, type 2 diabetes and BMI, the HOMA-IR × hypothyroidism interaction term was significant (OR = 3.01, 95% CI 1.03–8.82; likelihood-ratio p = 0.017). However, the finding did not survive Bonferroni correction across seven outcome/grouping combinations, and post-hoc power was 52%. This interaction should therefore be regarded as exploratory and hypothesis-generating, warranting replication in larger prospective multicenter cohorts.