The invention relates to calcium carbonate based compound micro particles and preparation and application thereof. The calcium carbonate based compound micro particles disclosed by the invention comprise calcium carbonate and a macromolecule stable layer, wherein the macromolecule stable layer comprises amphipathic molecules and / or hydrophilic molecules. The invention further discloses applicationof the calcium carbonate based compound micro particles to preparation of one or more of an adjuvant, a chemotherapy enhancing adjuvant, a radiotherapy enhancing adjuvant and a radiofrequency ablation treatment adjuvant for tumor immnuotherapy. The calcium carbonate based compound micro particles disclosed by the invention have an excellent effect of regulating a tumor slight acid environment, can reduce content of immunosuppressive cells in tumor, increase content of immune cells capable of killing the tumor and promote polarization of tumor-associated macrophages from the M2 type to the M1type, effectively turns the tumor immunosuppression micro environment, activate antitumor immunity, and can enhance a suppression effect of various treatment means of immunotherapy, chemotherapy, radiotherapy, radiofrequency ablation treatment and the like on tumor growth.