Significance The clinically silent intracellular development of Plasmodium parasites in the host liver is a prerequisite for the onset of malaria pathology. Liver stages can be completely eliminated by sterilizing immune responses and are promising targets for urgently needed antimalarial drugs and/or vaccines. The parasite is separated from the host cell cytoplasm by a parasitophorous vacuole (PV). We show that the PV membrane protein exported protein 1 interacts specifically with host Apolipoprotein H. The characterization of this protein–protein interaction revealed an essential role for both molecular partners during intrahepatic parasite growth. Our results improve our understanding of cell-biological aspects of host–pathogen interactions and may also help to develop new strategies to control Plasmodium infections.