In Taiwan, oral cancer has been the fourth leading cause of cancer-related deaths in men for at least a decade. Clinical statistics show that approximately 95% of all oral cancer cases are oral cavity squamous cell carcinoma (OSCC). Patients diagnosed with advanced-stage OSCC often present with cervical lymphatic or distant metastasis of cancer cells. The metastasis of OSCC results in a high mortality rate of the disease, indicating that the identification of proteins involved in the progression and/or metastasis of OSCC is important to develop novel strategies for OSCC treatments. To this end, five patient-derived xenograft (PDX) mouse models of OSCC have been established for understanding OSCC microenvironment and progression. Using isobaric tags for relative and absolute quantitation (iTRAQ)-based mass spectrometry, proteins in the tumor tissues of five OSCC patients and five PDX mouse models have been quantitatively profiled. Furthermore, we have determined gene expression profiles of the cancer tissues from four OSCC patients and four PDX mice using the RNA-Seq analyses. Candidate proteins consistently dysregulated in tumor tissues of primary OSCC and PDX mouse models would be selected for further evaluation as potential progression-related proteins and therapeutic targets of OSCC.