The hydrodeoxygenation (HDO) catalytic conversion of lignin has always been a hot research topic, and vacancy engineering is considered to be a new means to develop more efficient catalysts. Among them, oxygen vacancies and sulfur vacancies are widely used in HDO. Based on the current research status of vacancies in the field of lignin-derived oxygenates, this review discusses in detail the design methods of vacancy engineering, including surface activation, synergistic modification, and morphology control. Meanwhile, it is clarified that in the HDO reaction, vacancies can act as acidic sites, promote substrate adsorption and regulate product distribution, while for the catalysts, vacancies can enhance the stability and reducibility, improve metal dispersion, and improve the redox capacity. Finally, the characterization of vacancies is summarized, and feasible suggestions are proposed for the current deficiencies in this field.