Sensitive and reliable early diagnostic markers for oral squamous cell carcinoma (OSCC) remain unavailable. Early identification of recurrence for OSCC is also a challenge. This article reviews the recently identified biomarkers for OSCC such as cytokeratins, p53, tumor necrosis factor alpha (TNF-α), etc., which are of great utility in early diagnosis. In addition, the biomarkers that have been correlated with OSCC tumor malignancy by molecular pathology analysis are also described. This article speaks about selected reaction monitoring (SRM) which might even be applied to monitor differential expression of tumor proteins in blood, saliva, or fresh frozen tissue materials. SRM technique may complement or possibly replace western blotting for biomarker verification and for selection of potential biomarker candidates. This article may help to identify the potential biomarkers for screening and the molecular pathology analysis for high-risk patients of OSCC. Effective screening to identify high-risk patients will allow clinicians to provide an early and appropriate treatment to patients without delay and also reduce the risk of recurrence of OSCC.