Geometry optimization was carried out on neonicotinoid based on the crystal structure and molecular configuration of imidacloprid and the methyl substituent at N3 position of imidacloprid using a variety of methods and basis sets. Comparing the structural parameters obtained from calculation with the crystal structure data via AM1,RHF/631G, RHF/631G（d）and B3LYP/631G, B3LYP/631G(d) combined with the singlepoint energy, infrared spectroscopy and optimized CPU time, the result showed: the optimized CPU time of AM1, RHF/631G and B3LYP/631G were shorter, but the optimization was less effective; The optimization results of RHF/631G (d) and B3LYP/631G (d) were very consistent with the crystal conformation, among which the one obtained by B3LYP/631G was more accurate and consumed less CPU time than that obtained by RHF/631G (d). Therefore, B3LYP/631G (d) was the most appropriate method for studying quantum chemical and QSAR of the neonicotinoid compound.