Rashba spin splitting and quantum spin Hall effect have attracted enormous interest due to their great significance in the application of spintronics. According to the first-principles calculation, we propose a two-dimensional hexagonal lattice material H-Pb-Cl, which realizes the coexistence of giant Rashba spin splitting and quantum spin Hall effect. Owing to the break of space inversion symmetry and the existence of intrinsic electric field, H-Pb-Cl has a huge Rashba spin splitting phenomenon (α_R = 3.78 eV·Å), and the Rashba spin splitting of H-Pb-Cl(–16%—16%) can be adjusted by changing the biaxial stress. By analyzing the electronic properties of H-Pb-Cl, we find that H-Pb-Cl has a huge band gap near the Fermi surface (1.31 eV), and the topological invariant Z₂ = 1 of the system is caused by the inversion of s-p orbit, which indicates that H-Pb-Cl is a two-dimensional topological insulator with a huge topological band gap, and the gap is large enough to observe the topological edge states at room temperature. In addition, we further consider the effect of BN and graphane substrates on the topological band gap of H-Pb-Cl by using the H-Pb-Cl (111)-(1×1) /BN (111)-(2×2) and H-Pb-Cl(1×1)/ graphane (2×2) system, and find that the lattice mismatch between H-Pb-Cl (5.395 Å) and BN (2.615 Å) and between H-Pb-Cl (5.395 Å) and graphane (2.575 Å) are about 3% and 4.5%, respectively. According to our calculation results, H-Pb-Cl still retains the properties of topological insulator under the effect of spin orbit coupling, and is not affected by BN nor graphane. Our results show that the nontrivial topological band gap of H-Pb-Cl can be well preserved under both biaxial stress effect and substrate effect. In addition, H-Pb-Cl can well retain the nontrivial topological band gap under the stress of –16%–16%, and thus there are many kinds of substrate materials used to synthesize this material, which is very helpful in successfully realizing preparation experimentally. Our research provides a promising candidate material for exploring and realizing the coexistence of Rashba spin splitting and quantum spin Hall effect. And the coexistence of giant Rashba spin splitting and quantum spin Hall effect greatly broadens the scope of potential applications of H-Pb-Cl in the field of spintronic devices.