Chitosan with pH sensitivity and biocompatibility was selected to prepare chitosan nanoparticle-stabilized Pickering emulsion (CSPE). The flexibility of CSPE enables stress deformation when in contact with cell membranes, thereby mimicking the deformability of natural pathogens and facilitating their efficient uptake by cells. In the acidic environment of lysosomes, the amino groups of chitosan molecules are protonated, and the water solubility increases. CSPE transforms from particle-stabilized to polymer chain-stabilized, its subsequent swelling and proton accumulation lead to lysosome rupture. The experimental results evaluating CSPE as an adjuvant shows that CSPE could efficiently load antigens, promote endocytosis and antigen cross-presentation, recruit antigen-presenting cells at the injection site, boost T-cell activation, and enhance both humoral and cellular immune responses. In the prophylactic and therapeutic tumor models of E.G7-OVA lymphoma and B16-MUC1 melanoma, CSPE significantly inhibited tumor growth and prolonged the survival of mice. In summary, antigenic lysosomal escape resulted from the chitosan molecular state transition is the key to the enhancement of cellular immunity by CSPE, and CSPE is a promising vaccine adjuvant.