Cottonseed hull is a livestock feed with large daily consumption. If pesticide residues exceed the standard, it is easy for them to be introduced into the human body through the food chain, with potential harm to consumer health. A method for multi-residue analysis of 237 pesticides and their metabolites in cottonseed hull was developed by gas-chromatography and liquid-chromatography time-of-flight mass spectrometry (GC-QTOF/MS and LC-QTOF/MS). After being hydrated, a sample was extracted with 1% acetic acid in acetonitrile, then purified in a clean-up tube containing 400 mg MgSO4, 100 mg PSA, and 100 mg C18. The results showed that this method has a significant effect in removing co-extracts from the oily matrix. The screening detection limit (SDL) was in the range of 0.2–20 μg/kg, and the limit of quantification (LOQ) was in the range of 0.2–20 μg/kg. The recovery was verified at the spiked levels of 1-, 2-, and 10-times LOQ (n = 6), and the 237 pesticides were successfully verified. The percentages of pesticides with recovery in the range of 70–120% were 91.6%, 92.8%, and 94.5%, respectively, and the relative standard deviations (RSDs) of all pesticides were less than 20%. This method was successfully applied to the detection of real samples. Finally, this study effectively reduced the matrix effect of cottonseed hull, which provided necessary data support for the analysis of pesticide residues in oil crops.