Heterodera filipjevi, a major cereal cyst nematode (CCN), secretes effectors into plant cells to promote infection. Understanding the molecular mechanisms on how these effectors manipulate host targets is critical for deciphering the pathogenicity of CCNs. In this study, two venom allergen-like proteins, HfVAP1 and HfVAP2, from H. filipjevi, were identified, both of which contained functional signal peptides required for secretion and were exclusively expressed in the subventral esophageal gland cells of the nematodes. These two proteins were identified to suppress programmed cell death in Nicotiana benthamiana and interact with TaCAT3-A1, a key hydrogen peroxide-scavenging catalase in wheat. Notably, HfVAP2 stabilized TaCAT3-A1 and enhanced its enzymatic activity. Knockout of TaCAT3-A1 in wheat led to increased accumulation of reactive oxygen species (ROS), upregulation of pathogen-related (PR) genes and suppression of the jasmonic acid (JA) signal pathway, resulting in enhanced resistance to H. filipjevi. Our findings reveal that H. filipjevi secretes HfVAP2 to stabilize TaCAT3-A1, thereby suppressing ROS accumulation and PRs expression while activating the JA signal pathway to facilitate nematode infection. This study provides new insights into the molecular strategies employed by CCNs to manipulate host immunity.