Tumour cells undergoing immunogenic cell death (ICD) can elicit a specific anti-tumour immune response by releasing some specific signalling molecules, which determines the long-term success of cancer therapeutic strategies. In this study, human serum albumin (HSA) was hybridized with hemoglobin (Hb) by intermolecular disulfide bonds to develop a Ce6-loaded hybrid protein oxygen carrier (C@Hb/HSA). Then, the efficacy of C@Hb/HSA-mediated photodynamic therapy (PDT) in CT26.WT cells was assessed. Whether C@Hb/HSA-mediated PDT can induce the ICD was also studied. The results show that under laser irradiation, low-dose C@Hb/HSA exhibits enhanced reactive oxygen species generation in CT26.WT cells, leading to a low cell viability of (17.8±5.5)%. Meanwhile, C@Hb/HSA-mediated PDT dramatically increases the surface-exposure of calreticulin, thereby effectively enhancing the immunogenicity of CT26.WT cells and significantly promoting the maturation of dendritic cells.