Abstract: A rapid multi-residue analytical method for the simultaneous determination of mesotrione and MCPA-Na was developed using dispersive solid phase extraction and high performance liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS). The analytes were extracted by ethyl acetate, cleaned up by PSA and C18 solid phase extraction column, and separated on a reversed phase C18 column using a gradient elution program with 0.1% aqueous formic acid and 0.1% methanol formic acid as the mobile phase. Quantitative analysis was performed with electrospray ionization in positive/negative mode (ESI+)/(ESI-) under multiple reaction monitoring (MRM) mode. In this study, the LODs of mesotrione and MCPA were 0.005 ng and 0.025 ng, respectively, and LOQ were 0.01 and 0.05 mg/L, respectively. When the addition levels ranging from 0.001 to 2 mg/L mesotrione and from 0.005 to 5 mg/L MCPA, there was a good linear relationship between the mass concentration and the corresponding peak area, and the correlation coefficients were higher than 0.9997. When the addition level ranged from 0.01 to 2 mg/L, the average recovery of mesotrione in water, paddy soil, rice plant, rice husk and brown rice was 75%-103%, and the relative standard deviation (RSD) ranged from 0.1% to 8.2%; when it ranged between 0.05-10 mg/L, the average recovery rate of MCPA in water, paddy soil, rice plant, rice husk and brown rice rate was between 90%-113%, and the RSD was between 0.5%-7.4%. Results indicated that this method is highly efficient, with good sensitivity and accuracy, which can meet the detection requirements of mesotrione and MCPA residues in Oryza sativa ecosystem samples.