The nuclear genome of the human malaria parasite Plasmodium falciparum encodes a homolog of the bacterial HU protein (PfHU). In this study, we characterised PfHU's physiological function. PfHU, which is targeted exclusively to the parasite's plastid, bound its natural target--the plastid DNA--sequence-independently and complemented lack of HU in Escherichia coli. The HU gene could not be knocked-out from the genome of Plasmodium berghei, implying that HU is important for the parasite's survival. As the human cell lacks the HU homolog, PfHU is a potential target for drugs to control malaria.