Large-scale synthesis of Cu_2−xSe nanocrystals (nano-Cu_2−xSe) with uniform size was performed via a facile hydrothermal method at room temperature and at 120 °C. Nano-Cu_2−xSe with different structures could be synthesized by changing the reaction/growth time, the Cu:Se molar ratios, and the initial concentration of the precursors. The synthesized nano-Cu_2-xSe was characterized using various techniques, including x-ray powder diffraction, scanning electron microscopy and photocatalytic activity. Systematic studies showed that the reaction time played a key role in controlling the morphology and structure leading to significant influence on the photocatalytic activity of nano-Cu_2−xSe. With increasing reaction/growth time, Cu_2−xSe could transform gradually from a cubic to hexagonal structure and from nanoparticles to nanoplate/nanorod shapes. The photocatalytic characteristics were evaluated by the photo-decoloration of Rhodamine B (RhB) in aqueous solution under visible light irradiation. As-prepared nano-Cu_2−xSe showed good photocatalytic activity under visible light irradiation, indicating potential applications in depollution technologies.