Although Pb harbors a strong spin–orbit coupling effect, pristine plumbene (the last group-IV cousin of graphene) hosts topologically trivial states. Based on first-principles calculations, we demonstrate that epitaxial growth of plumbene on the BaTe(111) surface converts the trivial Pb lattice into a quantum spin Hall (QSH) phase with a large gap of ∼0.3 eV via a selective substrate-orbital-filtering effect. Tight-binding model analyses show the p_z orbital in half of the Pb overlayer is selectively removed by the BaTe substrate, leaving behind a p_z–p_x,y band inversion. Based on the same working principle, the gap can be further increased to ∼0.5–0.6 eV by surface adsorption of H or halogen atoms that filters out the other half of the Pb p_z orbitals. The mechanism of selective substrate-orbital-filtering is general, opening an avenue to explore large-gap QSH insulators in heavy-metal-based materials. It is worth noting that plumbene has already been widely grown on various substrates experimentally.