Introduction: Oral Potentially Malignant Disorders (OPMD) are chronic conditions that can progress to malignancy. Heat Shock Proteins (HSP) are a group of proteins that act as molecular chaperones. Actually, HSPs can promote the growth of tumor cells. On the other hand, they stimulate immune response against tumor cells. In this review it has been aimed to identify the role of HSP70 expression in the diagnosis and prognosis of OPMD. Methods: In this systematic review study, all English and Persian articles with the keywords of "oral lichen planus", " Leukoplakia ", " Oral Submucous Fibrosis ","heat shock protein 70", " oral premalignant disorders " along with their Persian equivalents were searched from Google scholar, PubMed, science direct, Cochrane, Scopus and Sid databases until March 2020. The quality of the selected studies were evaluated by the Newcastle-Ottawa scale method.  Results: Totally, 20 articles were selected and reviewed. The results of this study showed that there was an overexpression of HSP70 in OPMD. A significant correlation of HSP70 expression was observed with the severity of epithelial dysplasia. Actually, the expression of HSP70 can be a marker for the presence of dysplasia in OPMD. Conclusion: Enhanced HSP70 levels in pre-malignant and malignant cells suggests that not only the oncogenes and tumorsuppressor genes are involved in the process of oral carcinogenesis, but HSP70s may also be implicated in tumorigenesis. Taking all these into account, it can be supposed that in the future, HSP70 can be a target for an anticancer immunotherapy.