Nanomaterials have provided an emerging solution to improve the efficacy of cancer vaccines against malignant tumors. However, developing nanoparticles possessing both potent immunoadjuvant and co-delivery activities without tedious functionalization remains challenging. In the present work, we report that pristine benzene-bridged mesoporous organosilica nanoparticles are a novel immunoadjuvant and co-delivery platform for both antigen and cytosine-phosphodiester-guanine oligodeoxynucleotide (CpG, a toll-like receptor 9 agonist). It is shown that the chemical compositions of bridged organosilica framework (–Si–R–Si–OH, R = benzene, ethylene) have a significant impact on their functionalities. When benzene bridge groups are present in the framework, pristine nanoparticles with large mesopores and high pore volumes are able to stimulate the maturation of dendritic cells, and efficiently co-encapsulate ovalbumin (OVA) and CpG for delivery into immune cells, leading to a superior tumor inhibition performance in an aggressive OVA-expressed B16F10 melanoma model, with 100% tumor-free mice in 25 days. Our study provides new knowledge in the design of effective cancer nanovaccines.