Using waxy corn starch as raw material and stannous isooctanoate as catalyst, polylactic acid modified waxy corn starch was prepared in the melting system of lactide. A 1H-NMR method for determining the degree of substitution of polylactic acid modified waxy corn starch was established. With the degree of substitution as the response value, reaction time, reaction temperature and the amount of lactide as the investigation factors, the synthesis process of polylactic acid modified waxy corn starch was optimized through single factor and response surface experiments. The optimum process was obtained as follows: reaction time 12.46h, reaction temperature 111.75 ℃, lactide content 258% of starch. The predicted maximum degree of substitution is 0.0253, and the actual degree of substitution is 0.0238. Through a series of characterization of polylactic acid modified starch prepared under the optimal conditions, it is proved that the particle structure of polylactic acid modified waxy corn starch has not been completely destroyed, and its crystal form and molecular weight are better than those of traditional solvent technology. It will have a broad application prospect in the fields of degradable materials and drug carriers.