About 15 to 20% of the total Hsp70 is released to the extracellular space of some tumour cells, where it associates with cholesterol-rich microdomains located on the cell surface. Extracellular Hsp70 is known to recruit natural killer cells, leading to the concomitant release of granzyme B (GrB). This leads to the selective destruction of the tumour cells. A 14-mer TKD motif (KDNNLLGRFELSG) of human Hsp70 (hHsp70) is implicated in activating the NK cells. One of the defining features of Plasmodium falciparum, the most prevalent and lethal agent of malaria, is that it exports one of its Hsp70s, named PfHsp70-x, to the infected human red blood cell (RBC). In addition, hHsp70 is also present in the RBC. It has been reported that the infection of the RBC by the malaria parasite is associated with the migration of Hsp70 to the membrane of the host cell. Interestingly, GrB is elevated in severe malaria (SMA). PfHsp70-x, present on the outer leaflet of the infected RBC membrane, may stimulate NK cells to release GrB. We discuss the possible roles of Hsp70 and GrB in driving the development of SMA, and the prospects of Hsp70-GrB-mediated antimalarial therapy.