Fe:Co:ZnSe nanocrystals with different co-doping ratios of Fe2+/Co2+ ions were fabricated by hydrothermal synthesis. The facile method used in the present work avoids the mid-infrared quench effect induced by the organic molecular introduced in the past preparation process. These nanocrystals are spherical in shape and exhibit a cubic sphalerite structure with an average grain size of about 15 nm. Through the energy conversion between Co2+ and Fe2+ ions, mid-infrared fluorescences at 3.3 μm and 4.4 μm were detected under 1550 nm laser excitation at room temperature. The fluorescence band of 4.4 μm in the Fe:Co:ZnSe nanocrystals is thought to be an overlapping emission involving the peak centered at 4648 nm corresponding to the Co2+:4T1 (F) → 4T2 (F) energy transition and the peak centered at 4273 nm corresponding to Fe2+:5T2 (D) → 5E (D) energy transition. These high-quality optically active nanomaterials show potential applications in mid-infrared devices such as composite fiber-amplifiers and lasers materials. © 2020