Metal phosphorus trichalcogenides (MPTCs) are structurally adjustable 2D layered materials with unique electronic structures and high chemical diversity, implying the huge potential for energy storage application. In the typical electrochemical reaction process, rapid electron/ion conduction and abundant ion transport channels are the key parameters that influence the overall electrochemical performance of the electrode materials. Herein, 2D Cd1−xPS3Li2x nanosheets with enhanced mixed electronic/ionic conductivity are synthesized by the intercalation and vacancy strategy. The as-prepared thin-layered Cd1−xPS3Li2x electrode delivers high capacities of 1056 mAh g−1 at 0.2 A g−1 and 678 mAh g−1 at 8 A g−1, when used as anode in lithium-ion batteries. The variation of electronic structure and spatial layered structure in Cd1−xPS3Li2x induced by the synergistic effect of lithium-ion intercalation and Cd vacancies promote the dynamics of mixed electron/ion transport and offer more ion diffusion pathways, resulting in its excellent electrochemical performance. The strategy of mixed electron/ion conduction tuning for Cd1−xPS3Li2x can be extended to other MPTCs compounds to further develop their potential in the field of energy storage.