Nano CuO/ZSM-5 zeolite was prepared and used as a catalyst for dehydration of 1,4-butanediol (BDO) to tetrahydrofuran (THF) in liquid-phase. It was found that the 4.6 wt% CuO/ZSM-5 displayed good catalytic performance, and nearly 100% of BDO conversion and more than 99% of THF selectivity could be achieved by a rotary evaporator reactor at 170 °C under the atmospheric pressure. With such mild reaction conditions, 2400 g BDO could be converted to THF over 1 g catalyst under semi-continuous operation. Characterizations with X-ray diffraction (XRD), temperature-programmed reduction (TPR), NH₃-temperature programmed desorption (TPD), X-ray photoelectron spectroscopy (XPS), transmission electron microscope (TEM) and Brunauer-Emmett-Teller (BET) over fresh and used 4.6 wt% CuO/ZSM-5 were conducted. Based on the results of the characterization and catalytic performance of 4.6 wt% CuO/ZSM-5, it can be conjectured that the formed 1–3 nm CuO nanoparticles, suitable acidity of the catalyst due to the synergic interaction of CuO and ZSM-5 support promoted the dehydration of BDO to THF.