A matrix solid-phase dispersion (MSPD) method for the simultaneous determination of 20 organochlorine pesticides (OCPs) (aldrin, endrin, dieldrin, -BHC, -BHC, -BHC, -BHC, -chlordane, -chlordane, p,p -DDE, p,p -DDT, p,p -DDD, endosulfan I, endosulfan II, endosulfan sulfate, endrin aldehyde, heptachlor, heptachlor epoxide, endrin ketone and methoxychlor) and six polychlorinated biphenyl (PCB) congeners (PCB 28, 52, 101, 138, 153 and 180) in post-mortem human lung has been developed and validated. Response surface methodology (RSM) and desirability function were employed to optimize the extraction conditions of MSPD. Extraction was carried out using Florisil (2.0 g) as the sorbent material as well as clean-up adsorbent (1.5401 g), n-hexane:dichloromethane (11:89, v/v) as the eluting solvent (15.45 mL) and Na2SO4 (2.0 g) as dehydrating agent. Determination and quantification of OCPs and PCBs residues were carried out using a gas chromatograph equipped with an electron capture detector (GC-ECD). A mass spectrometric detector (GC-MS) in the selected ion monitoring (SIM) mode was also used for confirmation purposes. Method detection limits by GC-MS ranged from 0.42 to 0.87 ng gβ�’1 and 0.51 to 1.35 ng gβ�’1, for OCPs and PCBs, respectively. Lower detection limits were calculated for GC-ECD ranging between 0.15-0.30 ng gβ�’1 and 0.18-0.48 ng gβ�’1, respectively. Relative standard deviations did not exceed 9%. Analytes provided recoveries ranging from 65% to 106%. The proposed method was successfully applied to the analysis of lung tissues from six autopsy cases.