Using first-principles calculations, hydrogen evolution reaction (HER) activity on two-dimensional (2D) gallium chalcogenides monolayers GaX (X = O, S, Se, and Te) as well as the derived Janus monolayers Ga2XY (X≠Y, X/Y = O, S, Se, and Te) were systematically examined. It was found that Ga2OSe Janus monolayer with a 0.3% strain has the lowest ΔGH∗ of 0.19 eV (modified to −0.01 eV including the solvation effect) because (i) O is the most electronegative among X/Y atoms, (ii) the Ga2OSe monolayer has a larger lattice parameter with respect to GaO monolayer, and (iii) the built-in electric field is enhanced after H adsorption. The enhanced H adsorption with the lattice stretching is a result of the weaker Ga–O bond strength before H adsorption and the reduced electron fillings of anti-bonding molecular orbital formed by H 1s and O 2pz orbitals after H adsorption. The O-pz band center can be served as a descriptor to describe the HER activity trend for these p-block materials. Moreover, Ga2OSe monolayer has appropriate band alignment, distinguished optical absorption coefficient (105 cm−1), low exciton binding energy (0.71 eV), and the spontaneous HER process, indicating that it is a highly potential candidate for near-infrared photocatalyst for hydrogen production. Our research provides a novel paradigm that forming Janus structure can effectively tune the HER activity, which would guide the searching for excellent HER photocatalysts for clean hydrogen production.