PurposePrevious studies have suggested that cholesterol may influence thyroid function. Since statins are widely used for their cholesterol-lowering effect, we aimed to assess the association between statin use and thyroid function, and also to explore the role of the cholesterol-lowering effect in it.MethodsWe performed a retrospective cohort study derived from REACTION study. Eligible subjects receiving statin therapy were included in the statin group, and sex-, age-, total cholesterol (TC)-, and thyroid function-matched participants without lipid-lowering therapy were included in the control group. The median follow-up time was three years. Outcomes of thyroid function were evaluated at the end of follow-up. We used multivariable regression models to assess the association between statin use and outcomes of thyroid function, and also performed mediation analyses to explore the role of cholesterol in it.ResultsA total of 5,146 participants were screened, and 201 eligible subjects in the statin group and 201 well-matched subjects in the control group were analyzed. At the end of follow-up, TC and thyroid-stimulating hormone (TSH) levels in the statin group were lower than those in the control group (both p < 0.05), and the percentage of euthyroid subjects was higher in the statin group (88.06% vs. 76.12%, p = 0.002). The incidence rate of subclinical hypothyroidism (SCH) in euthyroid subjects was lower in the statin group (6.29% vs. 14.86%, p = 0.009), and the remission rate among subjects with SCH was higher in the statin group (50.00% vs. 15.38%, p = 0.008). In multivariable regression analyses, statin use was independently associated with lower TSH levels and higher odds to be euthyroid (OR 2.335, p = 0.004) at the end of follow-up. Mediation analyses showed the association between statin use and TSH levels were mediated by TC changes during follow-up.ConclusionStatin use was associated with benefits of thyroid function, and TC changes serve as a mediator of the association between statin use and TSH levels. Further studies are needed to clarify the possible underlying mechanism.