As greenhouse gases and environmental pollution become serious, the demand for alternative energy such as bioethanol has rapidly increased, and a large supply of biomass is required for bioenergy production. Lignocellulosic biomass is the most abundant on the planet and a large part of it, the second-generation biomass, has the advantage of not being a food resource. In this study, Sicyos angulatus, known as an invasive plant (harmful) species, was used as a raw material for bioethanol production. In order to improve enzymatic hydrolysis, S. angulatus was pretreated with different NaOH concentration at 121 °C for 10 min. The optimal NaOH concentration for the pretreatment was determined to be 2% (w/w), and the glucan content (GC) and enzymatic digestibility (ED) were 46.7% and 55.3%, respectively. Through NaOH pretreatment, the GC and ED of S. angulatus were improved by 2.4-fold and 2.5-fold, respectively, compared to the control (untreated S. angulatus). The hydrolysates from S. angulatus were applied to a medium for bioethanol fermentation of Saccharomyces cerevisiae K35. Finally, the maximum ethanol production was found to be 41.3 g based on 1000 g S. angulatus, which was 2.4-fold improved than the control group.