Malignant tumors are prevalent with high mortality rates in humans, dogs, and cats. Some microorganisms have been shown to inhibit cancer progression. The objective of this study is to evaluate the inhibitory effects of Neospora caninum, a livestock parasite, on three different tumor models in C57BL/6 mice, including Lewis subcutaneous tumors, Lewis and B16F10 melanoma lung metastasis. The results showed that a sufficient amount of N. caninum tachyzoites can significantly inhibit the development of subcutaneous tumors and lung metastasis (P <
0.002), and induce more than 50% tumor cell death in Lewis subcutaneous tumors. N. caninum treatment can significantly increases the infiltration of macrophages, NK cells, and CD8