Stony corals heavily rely on their intracellular algal symbionts for energetical supply. Increasing extreme weather driven by climate change often leads to disruption of the symbiosis and to coral death, threatening the sole existence of coral reefs, the key underwater ecosystems. As climate change mitigation outcomes are uncertain, it is important to search for ways to increase coral resilience towards future climate conditions, thermal extremes in particular. It has been shown that corals can withstand stress conditions better after previous exposure, but the mechanism remains unclear. Here we show that after three-day thermal preconditioning, stony coral Pocillopora acuta becomes more resilient to acute heat stress through modulations in cell signaling. In preconditioned corals, the expression of pro-survival gene pBcl-2 increases relatively to pro-death genes pBak and pBax during thermal stress, and the coral bleaching rate significantly decreases. After pBcl-2 activity inhibition, preconditioned corals lose the acquired beneficial phenotype and bleach at the same rate as non-preconditioned corals, which confirms the crucial role of programmed cell death in coral bleaching and acclimatization. The detailed analysis points to the involvement of autophagy/symbiophagy rather than apoptosis in the process. A similar shift in gene expression also occurs in thermally stressed corals that have previously acclimatized to summer temperatures in Kaneohe Bay, Hawai’i, suggesting that corals can naturally increase their resilience to warming events during high-risk periods through alterations in cell signaling. An in-depth understanding of molecular mechanisms underlying coral acclimatization and resilience could open the way for restoration practices such as human-assisted evolution.