The invention provides expression and purification methods of a fusion protein containing a recombinant human fibroblast growth factor 21 (hFGF21). In an expression process, the fusion protein is the fusion protein of GST protein and recombinant human fibroblast growth factor 21, is transferred into BL21 after being constructed into a plasmid with a GST tag, is subjected to IPTG induced expression, is greatly expressed in an inclusion body manner and is purified through ion-exchange column chromatography and a GST affinity column, and therefore a large quantity of high-purity proteins are obtained. The expression and purification methods have the beneficial effects that by expressing hFGF21 proteins by virtue of a GST system and optimizing induction conditions, the expression quantity of the proteins is substantially increased; by virtue of purification through the ion-exchange column chromatography and secondary purification through the GST affinity column, the loss of the proteins can be reduced as much as possible, and the purity of the proteins can be effectively improved; and the methods have important practical significance to the development of druggability of the hFGF21 proteins.