Maintaining the integrity of the plasma membrane after cellular damage is essential for cell survival. However, it is unclear how cells repair large membrane injuries in vivo. Here, we report that the tetraspanin protein, TSP-15, is recruited to large membrane wounds and forms a ring-like structure in C. elegans epidermis and promotes membrane repair after an injury. TSP-15 recruits from the adjacent region underneath the plasma membrane to the wound site in a RAB-5-dependent manner upon membrane damage. Genetic and live-imaging analysis suggested that the endosomal sorting complex required for transport III (ESCRT III) is necessary for recruiting TSP-15 from the early endosome to the damaged membrane. Moreover, TSP-15 interacts with and is required for the accumulation of t-SNARE protein Syntaxin-2, which facilitates membrane repair. These findings provide valuable insights into the role of the conserved tetraspanin TSP-15 in the cellular repair of large wounds resulting from environmental insults.