The goal of the current study was to investigate the expression of transient receptor potential vanilloid-1 (TRPV1) on human in vitro differentiated monocyte-derived dendritic cells (DCs) and to dissect the corresponding role of TRPV1-signaling in DC-specific functions. TRPV1 expression was identified both at the protein and gene levels in human DCs. Moreover, the prototypic TRPV1 agonist capsaicin specifically (i.e. via TRPV1) and dose-dependently inhibited cytokine-induced DC differentiation, phagocytosis of bacteria, activation of DCs, and pro-inflammatory cytokine secretion. These data introduce TRPV1-coupled signaling as a novel player in human monocyte-derived DC biology with anti-inflammatory actions.