Phagosome degradation is an evolutionally conserved and highly effective innate immune response against pathogen infections. The success of this process relies on the ability of phagocytes to regulate the maturation of phagosomes. However, the underlying molecular mechanisms and its roles in shaping downstream immune activation remain poorly understood. Here, we identify the proton-activated chloride (PAC) channel as a key negative regulator of phagosome maturation. PAC deletion enhanced phagosomal acidification and protease activities, leading to augmented bacterial killing in large peritoneal macrophages (LPMs) upon peritoneal