Oral cancer accounts for nearly 3% of all cancer cases and is becoming an increasingly frequent clinical problem in Asia. A strong tendency for loco-regional invasion and metastasis are the remarkable biological characteristics of OSCC，which is also a leading cause for the failure of treatment. Early stage of OSCC is defined as cT1-2N0M0. Operation is regarded as the first choice for treatment of OSCC. Excision of the primary tumor is essential with no doubt. However, surgical options for addressing the neck are contentious. The incidence of occult neck metastasis ranges from 8.5% to 45%, at average of 25.4%, while occult metastases can hardly be detected clinically or radiographically. If the neck dissection is not included in the therapy plan, the cN0 patients may experience increased mortality. However, the majority of early-stage OSCC patients, actually with no metastasis, may suffer from unnecessary iatrogenic injury and postoperative complications. Moreover, up to now, it is unclear for these cT1-2N0 OSCC, which are prone to metastasis. By integrating mass spectrometry (MS)-based proteomics with genomics and transcriptomics, we aim to investigate the different molecular features of primary lesions between pN0 and pN+.