Background:The incidence of Oral Cancer (OC) is high in Asian countries, which goes undetected at its early stage. The study of genetics, especially genetic networks holds great promise in this endeavor. Hub genes in a genetic network are prominent in regulating the whole network structure of genes. Thus identification of such genes related to specific cancer types can help in reducing the gap in OC prognosis. Methods: Traditional study of network biology is unable to decipher the inter-dependencies within and across diverse biological networks. Multiplex network provides a powerful representation of such systems and encodes much richer information than isolated networks. In this work, we focused on the entire multiplex structure of the genetic network integrating the gene expression profile and DNA methylation profile for OC. Further, hub genes were identified by considering their connectivity in the multiplex structure and the respective protein-protein interaction (PPI) network as well. Results: 46 hub genes were inferred in our approach with a high prediction accuracy (96%), outstanding Matthews coefficient correlation value (93%) and significant biological implications. Among them, genes PIK3CG, PIK3R5, MYH7, CDC20 and CCL4 were differentially expressed and predominantly enriched in molecular cascades specific to OC. Conclusions: The identified hub genes in this work carry ontological signatures specific to cancer, which may further facilitate improved understanding of the tumorigenesis process and the underlying molecular events. Result indicates the effectiveness of our integrated multiplex network approach for hub gene identification. This work puts an innovative research route for multi-omics biological data analysis.