Objective To investigate the clinical efficacy of selenium yeast tablets combined with levothyroxine sodium in the treatment of hypothyroidism and its effect on thyroid function and inflammatory factors. Methods 110 patients with primary hypothyroidism admitted to The first Affiliated Hospital of Yangtze University from January 2018 to December 2018, and were randomly divided into the observation group (55 cases) and the control group (55 cases). The patients of the control group were given sodium levothyroxine, while the observation group received selenium yeast tablets combined with levothyroxine sodium therapy. The indexes of thyroid function/clinical efficacy/adverse events were compared between the two groups. Results The total effective rate of the observation group was 92.73%, and 72.73% in the control group, there was a significant difference between the two groups (P<0.05). After treatment, T3, T4, FT3 and FT4 levels were significantly increased compared with that before treatment the differences were statistically significant (P<0.05). And TSH, TGAb and TPOAb levels were significantly lower compared with that before treatment, and the difference were statistically significant (P<0.05). After treatment, T3, T4, FT3 and FT4 degree of observation group were better than those of the control group, the differences were statistically significant (P<0.05). After treatment, the levels of IL-12 and IFN-γ in both groups decreased, but the levels of IL-12 and IFN-γ the observation group were lower than those in the control group (P<0.05). After treatment, the level of IL-10 increased in two groups, but the level of IL-10 in the observation group was higher than that of the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion The selenium yeast tablets combined with levothyroxine sodium in treatment of hypothyroidism can obtain obvious theraeputtic effects. which can not only improve the levels of various thyroid indexes, but also can improve patient's inflammatory factors levels, with good safety, without serious adverse reactions, therefor, which has important clinical application value. Key words: Selenium; Yeast Tablet; Hypothyroidism; Inflammatory Factor.