Reactive oxygen species (ROS) often injure intestinal epithelia that cause loss of damaged cells, which is mainly repaired by proliferation of intestinal stem cells (ISCs). To maintain the homeostatic state, coordination of sensing of the ROS injury and the subsequent epithelial cell loss with the replenishment by cell renewal is crucial. However, little is known about how gut epithelial cells initiate regenerative responses against ROS to maintain the tissue integrity. Here, we carried out a genome-wide screen, by which we identify immunoglobulin superfamily beaten path Ib (beat-Ib) as an essential gene for provoking ISC proliferation against ROS in Drosophila intestine. Interestingly, the beat-Ib function is required in differentiated enterocytes, the main targeted cells by ROS in the intestinal tract, but is dispensable in the stem cells. Moreover, beat-Ib is not involved in enterocyte apoptosis at ROS injury. These findings indicate the essential role of beat-Ib in Drosophila midgut enterocytes for initiating the non-cell-autonomous induction of ISC division in response to environmental ROS stresses.