Hookworms infect several hundred million people worldwide, causing malnutrition, anemia, and growth retardation. Infections generally result in a strong type 2 immune response, but the effector mechanisms that mediate worm expulsion remain poorly characterized. In this study, we determined the role of mast cells and basophils in protective immunity against the murine hookworm, Nippostrongylus Brasiliensis, during primary and secondary infection. Mast cell-deficient c-Kit(W-sh) mice had lower serum IgE levels compared with wild-type mice under steady-state conditions and after N. brasiliensis infection. Worm expulsion was delayed during primary but not during secondary infection of c-Kit(W-sh) mice, even in the absence of CD4 T cells. However, protective immunity was lost when basophils were depleted before reinfection of c-Kit(W-sh) mice. We conclude that basophils play a crucial role for worm expulsion during a memory type 2 immune response independently of mast cells and memory Th2 cells.