Hemozoin is a crystalline structure released from the detoxification of hemoglobin in Plasmodium falciparum-infected erythrocytes. Several studies have shown its effects on inflammation related to inflammasome activation, however its role in autophagy is still unclear. Here, we report that in response to hemozoin macrophages accumulate p62, leading to dysregulation of autophagy and enhanced inflammation. This was further confirmed by the decrease in LC3 II, a protein involved in autophagosome formation.