Abstract: Malaria remains a major global health challenge due to the continuous development of drug resistance to clinical therapeutics. Targeting host factors hijacked by malaria parasites, instead of parasite proteins, could circumvent the drug-resistance problem. However, only a few essential host factors have been identified. Using cell-based assays, this work shows that small-molecule inhibitors of host trafficking pathways impair parasite development in the liver stage. Phenotypic analyses upon genetic or pharmacological disruption indicate that host trafficking components are key modulators of parasite growth. These results suggest that Plasmodium parasites co-opt the host’s trafficking network, and implicate this pathway in the establishment of a successful infection. Future work will provide a mechanistic basis for this host-parasite interaction.