MXenes are a large family of two-dimensional (2D) early transition metal carbides that have shown great potential for a host of applications ranging from electrodes in supercapacitors and batteries to sensors to reinforcements in polymers. Here, on the basis of first-principles calculations, we predict that Mo2MC2O2 (M = Ti, Zr, or Hf), belonging to a recently discovered new class of MXenes with double transition metal elements in an ordered structure, are robust quantum spin Hall (QSH) insulators. A tight-binding (TB) model based on the dz2-, dxy-, and dx2-y2-orbital basis in a triangular lattice is also constructed to describe the QSH states in Mo2MC2O2. It shows that the atomic spin-orbit coupling (SOC) strength of M totally contributes to the topological gap at the Γ point, a useful feature advantageous over the usual cases where the topological gap is much smaller than the atomic SOC strength based on the classic Kane-Mele (KM) or Bernevig-Hughes-Zhang (BHZ) model. Consequently, Mo2MC2O2 show sizable gaps from 0.1 to 0.2 eV with different M atoms, sufficiently large for realizing room-temperature QSH effects. Another advantage of Mo2MC2O2 MXenes lies in their oxygen-covered surfaces which make them antioxidative and stable upon exposure to air.