In vivo experiments also confirmed that exogenous H2S provoked the M2 to M1 phenotypic transformation through S‐sulfhydrating GRP78 proteins to trigger the IRE‐1α‐ERS pathway, and exogenous administration of H2S decreased tumor burden, inhibited metastasis, and increased survival in subcutaneous transplantation mouse models of BC. This evidence concerns the gene HSPA5 and neoplasm.