We report a bio-inorganic hybrid system, [Mo154]@VLPs, constructed from the virus-like particles (VLPs) of the HPV capsid protein L1 and a giant disc-shaped, molybdenum-containing polyoxometalate of [Mo154]. The hybrid was purified by CsCl gradient centrifugation and further validated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), dynamic light scattering (DLS) and transmission electron microscopy (TEM). An assembly with [Mo154] improved the tolerance of VLPs to pH, temperature, and storage time, thereby defining an opportunity to reduce the cost of HPV vaccines. Moreover, the ability of [Mo154] to kill cancer cells was improved by 6% after being encapsulated inside the VLPs, which is mainly attributed to the enhanced biocompatibility of [Mo154]. The irradiation of both [Mo154] and [Mo154]@VLPs with an infrared light of 808 nm further enhanced their ability to destroy cancer cells by 3- and 2-fold, respectively, confirming that [Mo154] is an effective anti-tumor photo-thermal agent. Therefore, the successful hybrid of L1-p and [Mo154] improves the stability of VLPs and simultaneously paves the way to enhance the anti-tumor ability of [Mo154] and further extends its application prospects as a future anti-tumor drug.