Tomato gray mold (TGM), a worldwide destructive disease, is caused by Botrytis cinerea, and fungicide treatments are effective for its control. Pydiflumetofen is a new fungicide of succinate dehydrogenase inhibitors. In this research, 153 B. cinerea isolates were collected from eight different cities in Hebei Province from 2015 to 2017. The sensitivity of these 153 isolates to pydiflumetofen was determined by spore germination assays and mycelial growth rate assays. The results indicated that for these tested isolates, the EC₅₀ values of pydiflumetofen ranged from 0.0036 to 0.0822 mg/L (on conidia germination), and 0.0287–1.2659 mg/L (on mycelial growth rate), with average EC₅₀ values of 0.0327 ± 0.0213 mg/L and 0.3717 ± 0.2744 mg/L, respectively. The frequency distribution of the sensitivity of these 153 isolates to pydiflumetofen was a continuous single-peak curve, and could be used as the baseline for testing the sensitivity of B. cinerea to pydiflumetofen. No cross-resistance existed between pydiflumetofen and the other six botryticides such as diethofencarb, pyrimethanil, iprodione, pyrisoxazole, and fludioxonil, apart from fluopyram. The control efficacy of pydiflumetofen against TGM was determined using detached leaves and in field trials. Pydiflumetofen exhibited good control efficacy against TGM and the preventive effect was better than the curative effect. In the field trials, the control efficacy of pydiflumetofen against TGM was higher than 80%, both on leaves and fruits, at doses of 120, 160 and 200 g a.i./ha. It was significantly better than pyrimethanil. This study showed that pydiflumetofen had high activity and could effectively control the prevalence of TGM, but it should be administered carefully.