The invention provides a degradable polymer microsphere containing a gel core as well as a preparation method and an application of the polymer microsphere. The preparation method of the polymer microsphere comprises the following steps: dissolving a polymer PLGA (poly(lactic-co-glycolic acid)), PCL (polycaprolactone) or PLA (polylactic acid) in dichloromethane or ethyl acetate, so that a shell material is obtained; separately dissolving hyaluronic acid and hydroxyethyl chitosan in water, so that a hyaluronic acid solution and a hydroxyethyl chitosan solution are prepared, and then uniformly mixing the hyaluronic acid solution, the hydroxyethyl chitosan solution and bovine serum albumin or cytochrome C protein, so that a physical gel core material is obtained; and preparing the degradable polymer microsphere containing the gel core by virtue of a coaxial electrospray preparation process. The degradable polymer microsphere disclosed by the invention is relatively high in drug loading capacity and encapsulation efficiency; and the degradable polymer microsphere can serve as a carrier of protein or polypeptide hydrophilic drugs.