The innovative structural and compositional design of sulfur-loaded matrices is an effective strategy to improve the performance of lithium-sulfur batteries (LSBs). Herein, nanosized CeO2C2 with rich oxygen vacancies embedded in hollow mesoporous carbon composites (HMC/CeO2C2) were synthesized by hydrothermal and annealing reduction processes. This structure has several advantages: the large specific surface area and mesoporous carbon walls facilitate sulfur penetration and electron/ion transport; the abundant mesopores and hollow inner cavities provide the structural basis for sulfur storage and buffer its volume expansion; the oxygen vacancy-rich CeO2C2 nanoparticles grown in situ in HMC and in close contact with carbon form an electrically favorable CeO2C2/C heterointerface as an efficient catalyst, which is conducive to catalyzing the redox reaction of sulfur. Consequently, the retention capacity of the HMC/CeO2C2/S electrode is 728 mAh g−1 after 500 cycles at 0.5 C with a decay rate of 0.056 % per cycle, and it maintains a high reversible area capacity of 3.18 mAh cm−2 and excellent cycling performance even under a high sulfur loading of 4.7 mg cm−2. It provides an idea for the development of multifunctional sulfur-loaded materials with high sulfur loading, high conductivity, and high catalytic activity.