Apoptosis is considered a crucial part of the host defense system in oysters according to previous reports; however, the exact process by which this occurs remains unclear. Besides, mitochondrial apoptosis is the primary method of apoptosis in vertebrate cells, but has been poorly studied in invertebrates and is quite controversial. In this study, we investigated the molecular mechanism of mitochondrial apoptosis in the Pacific oyster Crassostrea gigas. Notably, we show that most key elements involved in the vertebrate mitochondrial apoptosis pathway - including mitochondrial outer membrane permeabilization, cytochrome c release, and caspase activation - are also present in C. gigas. In contrast, the lack of Bcl-2 homology 3-only subfamily members and apoptotic protease activating factor-1 (APAF-1) protein revealed evolutionary diversity from other phyla. Our results support that mitochondrial apoptosis in animals predates the emergence of vertebrates, but suggest that an unexpectedly diverse mitochondrial apoptosis pathway may exist in invertebrates. In addition, our work provided new clues for an improved understanding of how bivalve acclimate themselves to an inconstant environment.