Abstract: A simple and fast multi-residue method was established to simultaneously determine 56 pesticide residues, such as carbendazim, acetamiprid, and fipronil, in Lentinus edodes using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Samples were extracted with acidic acetonitrile and then cleaned up with a mixture of sorbents (PSA and C₁₈). Compounds were ionized using the electrospray ionization (ESI⁺) and operated in positive mode. Results showed that good linearity was achieved with a determination coefficient of 0.99. Recoveries ranged from 71% to 121% with relative standard deviation (RSD) of 0.6% to 9.2%, which were good enough for the routine analysis of the pesticide residues. The effect of solvents and filter membranes on the detection of L. edodes were also investigated. When the solvent contains a high proportion of  water phase, pyridaben and other compounds have a significant loss when filtered through the PTFE or nylon filter. The results of matrix effect study showed that 40 pesticides, such as methomyl, exhibited weak matrix effect. And 16 pesticides, such as methamidophos, showed moderate medium matrix effect. The method can be used as routine analysis method in multi-residual pesticide monitoring of L. edodes.