LESION SIMULATING DISEASE1 (LSD1) is an important negative regulator of programmed cell death (PCD) in Arabidopsis (Arabidopsis thaliana). The loss-of-function mutations in LSD1 cause runaway cell death triggered by reactive oxygen species (ROS). LSD1 encodes a novel zinc finger protein with unknown biochemical activities. Here, we report the identification of CATALASE3 (CAT3) as an LSD1-interacting protein by affinity purification and mass spectrometry-based proteomic analysis. The Arabidopsis genome contains three homologous catalase genes (CAT1, CAT2 and CAT3). Yeast two-hybrid and co-immunoprecipitation analyses demonstrated that LSD1 interacted with all three catalases both in vitro and in vivo, and the interaction required the zinc fingers of LSD1. We found that the CAT enzymatic activity was reduced in the lsd1 mutant, indicating that the catalase enzyme activity was partially dependent on LSD1. Consistently, the lsd1 mutant was more sensitive to catalase inhibitor 3-amino-1, 2, 4-triazole than wild type, suggesting that the interaction between LSD1 and catalases is involved in the regulation of the ROS generated in the peroxisome. Genetic studies revealed that LSD1 interacted with CAT genes to regulate the light-dependent runaway cell death and hypersensitive-type cell death. Moreover, the accumulation of salicylic acid was required for PCD regulated by the interaction between LSD1 and catalases. These results suggest that the LSD1-catalase interaction plays an important role in regulating PCD in Arabidopsis.