A high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS) method was established for the simultaneous determination of 498 farm chemical residues in Atractylodis Macrocephalae Rhizoma. Furthermore, the established method was used to determine the residues in 30 batches of Atractylodis Macrocephalae Rhizoma samples from different habitats. The samples were extracted with acetonitrile containing 1% glacial acetic acid, and the extract was purified by dispersive solid-phase extraction with sorbents of magnesium sulfate, primary secondary amine(PSA), C_(18), silica gel, and graphitized carbon black(GCB). The prepared samples were then analyzed by HPLC-MS/MS, and the internal standard method was used to quantify the residues. The experimental results showed that the 498 farm chemicals presented good linear relationship within the range of 5-400 ng·mL~(-1), with correction coefficients greater than 0.990. Within the linear ranges, the recovery of 495 farm chemicals(except daimuron, chinomethionat, and emamectin benzoate) at three spiked levels(0.05, 0.10, and 0.20 mg·kg~(-1)) was in the range of 61.18%-132.1%, with the RSD of 0.24%-15%. A total of 16 farm chemicals were detected in 30 batches of samples. Among them, difenoconazole and tebuconazole showed higher detection rates, and the detection rate of difenoconazole was 76.7%. The residues of 4 batches of samples exceeded the limits of quantitation of 33 banned farm chemicals stipulated in the Chinese Pharmacopoeia. The theoretical maximum residue limits of the farm chemicals except banned farm cheimicals were used as the judgment standard of safety risks, under which the detected residues of clothianidin, difenoconazole, and pirimiphos-methyl exceeded the theoretical maximum residue limits. The new method established in this paper is simple and reliable, and it can thus be used for qualitative and quantitative analyses of farm chemical residues in Atractylodis Macrocephalae Rhizoma.