MoV2O8 micro-cuboids were environment-friendly prepared via a facile one-step solvothermal route followed by thermal treatment with vanadium pentoxide and ammonium molybdate as raw materials without using harmful solvents or surfactants. Characterization by XRD, FTIR, XPS, SEM and TEM showed that MoV2O8 formed a layered structure by the stacking of nanosheets and assumed a micro-cuboid shape with a thickness of 150∓30 nm, a width of 350∓110 nm and a length of 680∓18 nm. For the first time, the catalytic properties of MoV2O8 micro-cuboids were investigated for the gas-phase ammoxidation of p-chlorotoluene (PCT) to p-chlorobenzonitrile (PCBN). The as-prepared catalyst exhibited high activity and selectivity in the ammoxidation of PCT to PCBN, with a near 100% conversion and 83.6% yield.Graphical abstract: