BACKGROUND AND AIM: Oral lichen planus (OLP) is a chronic, autoimmune, inflammatory disease. The progression of OLP to oral squamous cell carcinoma (OSCC) has generated a longstanding controversy about the details of this malignant transformation potential. This study aimed to do a systematic review on the molecular markers related to the malignant transformation of OLP.METHODS: We searched the databases PubMed, Google Scholar, Science Direct, Scopus, Cochrane and Thomson Reuters Web of Science (1990-2015) with the MeSH key words of: (“oral lichenoid reaction”, “oral lichenoid lesion”, “oral lichenoid eruption”, “oral lichen planus” “lichen planus”, “lichenoid”) AND (“malignant transformation”, “premalignant character”, “cancerization”, “pre-neoplasm”, “squamous cell carcinoma”). The reviewers screened the identified publications in three steps according to title, abstract and full text, extracted all the investigated markers in screened articles and finally classified the markers according to the frequency. Extracted data were saved in Excel software.RESULTS: Out of 570 articles, 66 were finally enrolled in the study. The most frequent evaluated markers were p53, cyclooxygenase-2 (COX-2), Ki67, B-cell lymphoma-2 (Bcl-2), Bax, p21, and caspase-3.CONCLUSION: The present study concluded that there were some documented evidences for association between malignant transformation of OLP and seven molecular markers (p53, COX-2, Ki67, Bcl-2, Bax, p21, and caspase-3).