Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) is one of the most widely used powerful explosives. The direct and selective detection of HMX, without the requirement of specialized equipment, remains a great challenge due to its extremely low volatility, unfavorable reduction potential and lack of aromatic rings. Here, we report the first chemical probe of direct identification of HMX at ppb sensitivity based on a designed metal-organic cage (MOC). The cage features two unsaturated dicopper units and four electron donating amino groups inside the cavity, providing multiple binding sites to selectively enhance host-guest events. It was found that compared to other explosive molecules the capture of HMX inside the cavity would strongly modulate the emissive behavior of the host cage, resulting in highly induced fluorescence “turn-on” (160 folds). Based on the density functional theory (DFT) simulation, the mutual fit of both size and binding sites between host and guest leads to the synergistic effects that perturb the ligand-to-metal charge-transfer (LMCT) process, which is probably the origin of such selective HMX-induced turn-on behavior. Direct identification of HMX at ppb sensitivity based on a designed metal-organic cage was developed. Capture of HMX inside the cavity strongly induced fluorescence “turn-on” (160 folds) due to mutual fit of both size and binding sites between host and guest, leading to synergistic effects that perturb ligand-to-metal charge-transfer process. Display omitted