Malaria is among the most serious infectious diseases affecting humans, accounting for approximately half a million deaths each year1.Plasmodium falciparumcauses most life-threatening cases of malaria. Acquired immunity to malaria is inefficient, even after repeated exposure toP. falciparum2, but the immune regulatory mechanisms used byP. falciparumremain largely unknown. Here we show thatP. falciparumuses immune inhibitory receptors to achieve immune evasion. RIFIN proteins are products of a polymorphic multigene family comprising approximately 150–200 genes per parasite genome3that are expressed on the surface of infected erythrocytes. We found that a subset of RIFINs binds to either leucocyte immunoglobulin-like receptor B1 (LILRB1) or leucocyte-associated immunoglobulin-like receptor 1 (LAIR1). LILRB1-binding RIFINs inhibit activation of LILRB1-expressing B cells and natural killer (NK) cells. Furthermore,P. falciparum-infected erythrocytes isolated from patients with severe malaria were more likely to interact with LILRB1 than erythrocytes from patients with non-severe malaria, although an extended study with larger sample sizes is required to confirm this finding. Our results suggest thatP. falciparumhas acquired multiple RIFINs to evade the host immune system by targeting immune inhibitory receptors.