The intestinal epithelium is the fastest renewing tissue in mammals and its regenerative process must be tight control to minimize the risk of dysfunction and tumorigenesis. The orderly expression and activation of the YAP protein is key initial step in driving intestinal development and crucial for intestinal regenerative responses and homeostasis. However, the regulatory mechanisms controlling this process remain largely unknown. Here, we discovered that evolutionarily conserved signaling intermediate in Toll pathways (ECSIT), a multi-functional protein, was enriched along the crypt-villus axis. And intestinal cell-specific ablation of ECSIT results in the dysregulation of intestinal epithelial cell (IEC) differentiation accompanied with enhanced YAP protein translation thus inducing spontaneous intestinal inflammation and augmenting intestinal tumorigenesis. We further revealed that loss of ECSIT disrupts mitochondrial metabolism thus reprograming to amino acid-based metabolism, which results in demethylation of genes encoding the eIF4F pathway and their increased expression that further promotes selective YAP translation initiation culminating in intestinal homeostasis imbalance and tumorigenesis. We also show that the expression of ECSIT is positively correlated with the survival of patients with colorectal cancer. Together, our studies demonstrate an important role of ECSIT in maintaining optimal intestinal homeostasis and controlling the development of tumorigenesis by regulation of the YAP protein translation through mitochondrial metabolism.