Field experiments were carried out at Sidi-Salem district, Kafr El-Sheikh Governorate, Egypt during seasons 2017 and 2018 to evaluate the efficacy of nine chemical compounds viz., thiamethoxam, acetamiprid, flonicamid, emamectin benzoate, methomyl, alpha-cypermethrin, profenofos, Kz-oil, and detergent soap against the cotton mealybug, Phenacoccus solenopsis Tinsley. The side effects of the tested compounds on the associated predatorswere studied as well. The obtained results revealed that profenofos and thiamethoxam were the most affective against cotton mealybug recording 82 and 79.4 % reduction respectively as mean of effect during 10 days experiment period in 2017. In 2018, thiamethoxam was the most potent followed by flonicamid and profenofos causing mean of reduction percentage in mealybug population by 78, 76 and 74, respectively. Whereas, emamectin benzoate, Kz-oil, and detergent soap had the lowest activity against mealybug in both seasons of study. The other tested compounds indicated a moderate toxicity. Concerning the side effects on the associated predators, profenofos, alpha-cypermethrin, thiamethoxam and flonicamid were the most harmful to Chrysoperla carnea Steph., and Coccinella undecimpunctata Linnaeus, recording more than 50 % mean of reduction. On the other hand, emamectin benzoate, Kz-oil, and detergent proved to be the most harmless to both predators having less than 25 % mean of reduction in the predators population.