The capsule associated protein 10 gene (CAP10) is indispensable to the formation of the polysaccharide capsule, and is closely associated with Cryptococcus (C.) neoformans virulence. In this study, we designed the shRNA expression plasmid to interfere with the synthesis of CAP10 gene. We infected mice with yeast cells in the respiratory tract, and monitored the development of infections in lung tissues. Results showed that the cap10-shRNA group may alleviate pathological lesions in pulmonary C. neoformans infection, and a lower degree of inflammatory cells was observed in the cap10-shRNA group. Moreover, the fungal burden was significantly lower in the cap10-shRNA group, indicating that the clearance towards C. neoformans was somehow affected. Down-regulation of CAP10 was beneficial to the balance of Th1/Th2 and Th17/Treg ratios. Collectively, our results showed that the expression of CAP10 was associated with an antifungal immune response in mice, suggesting that CAP10 regulates the inflammatory response. Therefore, we expect that the CAP10 gene will become a new molecular therapeutic target in cryptococcosis treatment.