Hv1s are ubiquitous highly selective voltage-gated proton channels involved in male fertility, immunology, and the invasiveness of certain forms of breast cancer. The mechanism of proton extrusion in Hv1 is not yet understood, while it constitutes the first step toward the design of high-affinity drugs aimed at this important pharmacological target. In this contribution, we explore the details of the mechanism via an integrative approach, using classical and QM/MM molecular dynamics simulations of a monomeric hHv1 model. We propose that protons localize in three binding sites along the channel lumen, formed by three pairs of conserved negatively charged residues lining the pore: D174/E153, D112/D185, and E119/D123. Local rearrangements, involving notably a dihedral transition of F150, a conserved phenylalanine lining the permeation pathway, appear to allow protons to hop from one acidic residue to the next through a bridging water molecule. These results constitute a first attempt at rationalizing hHv1 selectivity for H+ and the role played by D112 in this process. They pave the way for further quantitative characterization of H+ transport in hHv1.