A rapid method for the determination of simazine residue in sugarcane by matrix solid phase dispersion (MSPD) extraction and florisil cleanup was developed. This method performed extraction and cleanup in a single eluting step and significantly reduced organic solvent consumption. Two grams of homogenized sample was blended with 2 g of EnvirElut sorbent until a homogeneous mixture was observed. The mixture was transferred into a florisil cartridge, and eluted with 25 mL of dichloromethane. The eluate was evaporated to dryness, and the residue was dissolved with acetonitrile and then determined by HPLC-UV at 230 nm. Recoveries of simazine spiked in sugarcane (0.1~0.5 ppm) were determined to be 86.9~94.7%, while coefficient of variation was determined to be less than 10%. The detection limit was 0.02 ppm.