Valleytronics that relies on the valley degree of freedom is attracting growing interest because it provides a new platform for information storage. One obstacle in this field is to realize valley polarization in an efficient route to manipulate the valley physics. Here we propose a strategy to induce valley polarization by nonmetal atom doping in single-layer Tl2O. Owing to the intrinsic inversion asymmetry and large spin-orbit coupling, there are a two-fold valley degeneracy and an excellent spin-valley independence in single-layer Tl2O. Upon introducing C/N atoms in single-layer Tl2O, the intriguing valley polarization successfully appears, and the obtained polarization strengths are considerable. In particular, for N-doped case, the top valence band locates around the Fermi level, and there are no impurity states in the band gap, which is desirable for practical applications. It is predicted that these valley polarizations can be effectively engineered under the magnetic field and external strain, suggesting that the control of valley physics in single-layer Tl2O is accessible.