The invention belongs to the field of biological pharmacy, relates to application of a recombinant sfrp5 protein in preparation of medicines for treating nonalcoholic steatohepatitis and particularlyrelates to application of the recombinant sfrp5 protein in preparation of medicines for improving inflammations and fatty pathological changes of nonalcoholic steatohepatitis. Experiment results showsthat mice induced by methionine and choline deficient diet (MCDD) can be used for successively preparing animal models of nonalcoholic steatohepatitis; the experiment results also show that the intervention of the recombinant sfrp5 protein can reduce the inflammation damage and the fatty pathological changes of liver tissues of the animal models of nonalcoholic steatohepatitis, so that the inflammations and fatty pathological changes of nonalcoholic steatohepatitis can be reduced; the action mechanism of the recombinant sfrp5 protein is related to inhibition of activation of kupffer cells andinterdiction of WNT-TLR channels; the recombinant sfrp5 protein can be used for preparing the medicines for treating the nonalcoholic steatohepatitis.