Lettuce drop disease caused by Sclerotinia sclerotiorum is an epidemic plant disease and there are urgent economic incentives to control it in ways consistent with the sustainable approach. The study aimed to isolate Trichoderma species from the healthy rhizosphere of lettuce and identify and characterize the most effective isolate against fungal growth and sclerotia. Six isolates of Trichoderma were obtained while the isolate QLZ-2 showed high activity in its antagonism towards S. sclerotiorum in the laboratory. The isolate QLZ-2 was identified as Trichoderma asperellum by morphological and microscopic diagnosis. The laboratory experiment revealed that the isolate QLZ-2 spreads on the surface of sclerotia during the fungal mycoparasitism process in the soil of the dishes. On the other hand, the pot experiment showed that spraying the conidial suspension of the isolate QLZ-2 reduced the symptoms of lettuce fall disease. The severity of lettuce drop disease was reduced by 14.79% compared severity of disease in the water-only spray treatment, which had a 100%.