BACKGROUND: Pesticides have been widely used to control pests on agricultural products in China, and large amounts of pesticide residues have caused a serious threat to human health. Thus, developing a high-efficiency pesticide degradation method for fresh vegetables represents a great challenge. The present study investigated the effects of dielectric barrier discharge (DBD) plasma on the degradation of malathion and chlorpyrifos in aqueous solutions and on lettuces. RESULTS: DBD treatment significantly degraded malathion and chlorpyrifos in water and on lettuce. After cold plasma treatment at 80 kV for 180 s, the degradation efficiency of malathion (0.5 ∼g mL −1) and chlorpyrifos (1.0 ∼g mL −1) in aqueous solutions reached 64.6% and 62.7%, respectively. The degradation intermediates were explored by HPLC-mass spectrometry and the DBD plasma degradation pathways of malathion and chlorpyrifos were proposed. There was no significant damage to the quality of lettuces, including color and chlorophyll content, after plasma treatment. Ascorbic acid decreased significantly during long-term treatment with DBD plasma. To ensure the quality of lettuces during processing, the treatment time was shortened to 120 s. Under this condition, the degradation efficiency of malathion (0.5 mg kg −1) and chlorpyrifos (1.0 mg kg −1) on lettuces was found to be 53.1% and 51.4%. More importantly, we noted that cold plasma treatment significantly inactivated the microorganisms on lettuces. CONCLUSION: The results of the present study show that cold plasma is an effective and safe method for the degradation of organic pesticide residues on fresh vegetables at the same time as retaining the original quality.