Very recently, the centimeter-scale MoSi2N4 monolayer was synthesized experimentally and exhibited a semiconducting nature with high mobility (Hong et al., Science, 2020, 369, 670–674). Here, we show that MoSi2N4 and its analogues, MoSi2P4 and MoSi2As4, are potential two-dimensional (2D) materials for valleytronics based on first-principles calculations. We demonstrate that the intrinsic inversion symmetry breaking and strong spin–orbital coupling lead to the remarkable spin–valley coupling in the inequivalent valleys at K and K′ points, which result in not only the valley-contrasting transport properties, but also the spin and valley coupled optical selection rules. Moreover, the in-plane strain can tune the bandgaps and spin splitting or even induce an indirect-to-direct bandgap transition for promising application in the strain-tunable valleytronics. We find that the valley polarization can be generated by doping magnetic element. Our findings offer theoretical insight into the exotic physical properties of novel MoSi2N4-family materials beyond transition metal dichalcogenides.