The immunogenicity and cross-protection of Pneumococcal surface protein A (PspA) and its conjugates with polysaccharide were researched in mice injected with PspA and its conjugates respectively. The enzyme-linked immunosorbent assay (ELISA) was adopted to detect the immunogenicity of the antigen. Passive and active protection experiments against intraperitoneal challenge with Pneumococcal pneumonia were carried out to validate the protection of PspA and the conjugates with polysaccharide. The experimental results showed that the immune effects of both the conjugates and PspA were effective to against invasion of Pneumococcal pneumonia in mice (P < 0.01). And the conjugates of PspA with polysaccharide gave the best protection and survived 3 days longer than that of PspA. The conjugates with polysaccharide enhanced the higher level of both IgG and IgG2a antibody titer than that of PspA. The cross-reactivity of Western-blotting showed conjugates with polysaccharide caused immune reaction in different serological Pneumococcal pneumonia, this meant that the conjugates had some cross-protection function against different serotypes 6B, 5, 1, 23F, 19F. The conjugates of PspA with polysaccharide showed better immunocompetence and immune protection against invasion of Pneumococcal pneumonia than PapA and the capsule polysaccharide. This study demonstrated that the conjugates could enhance protection against Pneumococcal pneumonia, which should be pertinent to future efforts to develop new protein-based complex vaccines.