A new inorganic–organic hybrid In₂Se₃(en) was synthesized as hollow nanospheres via a facile and controllable hydrothermal method in a system containing ethylenediamine (en) and hydrazine hydrate. These as-obtained hybrid hollow nanospheres with an average diameter of 200 nm were assembled by irregularly small-sized (ca. 20 nm) nanoparticles. These hollow nanospheres were characterized by powder X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA). The surface chemical composition of the In₂Se₃(en) hollow nanospheres were studied by X-ray photoelectron spectroscopy (XPS). The possible gas bubble-template growth mechanism is proposed to understand the formation of In₂Se₃(en) hollow nanospheres. Room-temperature UV-vis diffuse reflection spectra and photoluminescence (PL) spectra indicate that the as-obtained hybrid nanospheres possess a maximum absorption at 470 nm and single strong near-infrared emission peak centered at 1092 nm. The near-infrared luminescence endows the hybrid nanospheres with potential application in telecommunications, biolabeling and biomedical imaging, etc.