Abstract: Solanum lycopersicum L. is one of the most widely cultivated cash crops globally, but its susceptibility to gray mold (Botrytis cinerea) causes significant economic losses. ERF transcription factors play a key role in plant stress responses. In this study, SlERF.F4 overexpression lines were generated and compared with wild-type tomato variety ‘AC’ (‘Ailsa Craig’) fruits to investigate the role of SlERF.F4 in mediating resistance to gray mold in tomatoes. Compared with ‘AC’ fruits, SlERF.F4-overexpressed (SlERF.F4-OE) fruits exhibited enhanced resistance to B. cinerea, as indicated by a slower lesion expansion following inoculation. Physiological and biochemical analyses revealed that the production rate of reactive oxygen species (ROS), including O₂^-. and H₂O₂ content, as well as malondialdehyde (MDA) levels, were significantly lower in SlERF.F4-OE fruits than in ‘AC’ fruits. Concurrently, antioxidant enzyme activities, including peroxidase (POD), catalase (CAT), and superoxide dismutase (SOD), were significantly elevated in SlERF.F4-OE fruits. In addition, phenylalanine ammonia-lyase (PAL) activity was higher in SlERF.F4-OE fruits than in ‘AC’ fruits. These results suggest that SlERF.F4 enhances resistance to B. cinerea in S. lycopersicum fruits by regulating reactive oxygen homeostasis and defense enzyme activity. This study provides novel insights into the function of SlERF.F4 in fruit disease resistance.