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• Residue behavior/processing factors of chlordecone assessed on four cooking processes. • ID-HPLC-MS/MS or LC-HRMS/MS used for target, suspect screening or untargeted approaches. • A significant decrease of CLD in bovine meat observed after microwave cooking process. • Traces of 5b-hydro-CLD and mono-hydro-CLD found in the uncooked liver. • No degradation by-product of CLD observed in the cooked liver. Chlordecone (CLD) is a toxic organochlorine pesticide frequently used in the French West Indies until 1993, resulting in a contamination of soil and food. This study assessed the behaviour of CLD residues and CLD processing factors (PFs) during four home cooking processes: cooking in a conventional oven ("oven"), frying ("pan"), cooking in a microwave oven ("microwave") and grilling ("grill"). These four processes were applied to six types of naturally contaminated beef (kidney, liver, rib, chuck, top-sirloin and sirloin). Targeted analyses with isotopic dilution were carried out by ID-HPLC-MS/MS to determine CLD concentrations before and after each cooking process and the corresponding processing factors. HPLC-HRMS/MS was used to find potential organochlorine degradation by-products and/or CLD metabolites present in samples by target, suspect and non-target screening. Cooking processes and especially microwave cooking led to a significant decrease in the CLD contained in beef (2% < PF < 17%). Traces of 5b-hydro-CLD and of another mono-hydro-CLD were found in the uncooked liver but no CLD degradation by-product was observed in the cooked liver. [ABSTRACT FROM AUTHOR]