Significance With more than 200 million cases per year worldwide and more than 400,000 deaths, mostly affecting children in sub-Saharan Africa, malaria is still one of the most prevalent infectious diseases. Infection with the malaria parasite Plasmodium falciparum is characterized by high inflammation but also the failure of the immune system to form efficient memory, leading to recurring infections. No efficient vaccine is available to date. Here we have studied the response of dendritic cells (DCs), an essential cell type in the orchestration of immune and vaccine responses. We found that P. falciparum induces a distinct transcriptional profile compared with a classical inflammatory stimulus in primary human DCs, leading to a highly atypical response, which may contribute to parasite immune evasion during malaria.