A “two-step method” was adopted to improve the hygienic property of polyamide microfiber synthetic leather base. Firstly, the amino-terminal hyperbranched polyamides (NH2-HBP) synthesized by N, N’-methylene bisacrylamide (MBA) and diethylene triamine (DETA) was cross-linked to microfiber synthetic leather base pretreated with formic acid, in which glutaraldehyde was the crosslinking agent. Secondly, Gelatin hydrolysate was cross-linked to the preliminary modified microfiber synthetic leather base by using glutaraldehyde as the crosslinking agent. The modified microfiber synthetic leather base was then obtained. Hygienic performances, mechanical properties, and the micro morphology were taken as indexes to optimize the dosages of glutaraldehyde and NH2-HBP.