Sono-immunotherapy is expected to effectively enhance treatment efficacy and reduce mortality in patients with pancreatic cancer. Hence, efficient applicable sono-immunotherapy systems are urgently needed for the treatment of this condition. In this study, hollow mesoporous carbon (HMC) nanoparticles were prepared using the sacrificial template method. These nanoparticles had a porphyrin-like structure and could generate singlet oxygen more efficiently than commercial TiO. Cellular assays showed that HMC killed tumor cells in the presence of ultrasonication, primarily by inducing apoptosis. HMC could also accelerate the release of immune factors by tumor cells, thereby activating dendritic cells and enhancing the efficacy of immunotherapy. Experiments in tumor-bearing mice and in situ pancreatic cancer tests showed that HMC, in combination with the small-molecule inhibitors of programmed cell death ligand 1, could reduce tumor growth via the generation of reactive oxygen species following ultrasonication. HMC could enhance the efficacy of immunotherapy by disrupting the immunosuppressive tumor microenvironment and promoting the accumulation of immune cells. Accordingly, in vivo sono-immunotherapy was achieved, and the growth of transplanted tumors and in situ tumors could be reduced. In conclusion, this study proposes a novel method for the preparation of HMC nanoparticles and demonstrates their potential in tumor treatment. Additionally, owing to their unique structure, these HMC nanoparticles could be used for different combination therapies tailored based on specific clinical requirements.