•Two novel Trichinella spiralis proteins aminopeptidase P and cathepsin X were expressed.•rTsAPP/rTsCX elicited systemic humoral response and gut mucosal sIgA response.•rTsAPP/rTsCX also induced a systemic and local mixed Th1/Th2 response.•rTsAPP+rTsCX provided a higher immune protection than rTsAPP or rTsCX alone.•TsAPP and TsCX might be considered novel candidate targets for anti-Trichinella vaccine. Trichinella spiralis is a major foodborne zoonotic parasitic nematode which has a serious threat to meat food safety. Development of anti-Trichinella vaccine is requisite for control and elimination of Trichinella infection in food animals to ensure meat safety. Aminopeptidase P (TsAPP) and cathepsin X (TsCX) are two novel proteins identified in T. spiralis intestinal infectious L1 larvae (IIL1). The objective of this study was to investigate the protective immunity elicited by immunization with TsAPP and TsCX alone and TsAPP-TsCX in combination in a mouse model. The results demonstrate that subcutaneous vaccination of mice with rTsAPP, rTsCX or rTsAPP + rTsCX elicited a systemic humoral response (high levels of serum IgG, IgG1/IgG2a and IgA) and significant local gut mucosal sIgA responses. The vaccination with rTsAPP, rTsCX or rTsAPP + rTsCX also induced a systemic and local mixed Th1/Th2 response, as demonstrated by clear elevation levels of IFN-γ and IL-4 in vaccinated mice. Vaccination of mice with rTsAPP+rTsCX exhibited a 63.99 % reduction of intestinal adult worms and 68.50% reduction of muscle larva burdens, alleviated inflammation of intestinal mucosal and muscle tissues, and provided a higher immune protection than that of vaccination with rTsAPP or rTsCX alone. The results demonstrated that TsAPP and TsCX might be considered novel candidate target molecules for anti-Trichinella vaccines.