Profenofos resistance was found in field strains of the pink bollworm, Pectinophora gossypiella (Saunders) collected at late season of 2013 from four Governorates in Egypt. Resistance was high in regions where profenofos were frequently used. Resistance ranged between 31.31 and 59.60% in the tested strains. Profenofos resistance was the highest in the individuals collected from Gharbia Governorate as compared with the other field strains; whereas the lowest resistance percentage was noticed in individuals collected from Kafrel-Sheikh Governorate. Studies carried out through estimation of the detoxification enzymes activity indicated that enhanced acetylcholinesterase, alkaline & acid phosphatases and α & β nonspecific esterases as well as total protein contents were probably important mechanisms for profenofos resistance in field strains. Colorimetric assays showed a significant positive correlation between increased resistance to profenofos in strains of P. gossypiella examined and the hydrolytic enzymes activity. The information presented illustrates the importance of proper Integrated Pest Management programs (IPM) to avoid the consequences associated with improper insecticide used.