Oral lichen planus (OLP) is a chronic inflammatory disorder with increased risk for malignant transformation. Biomarker validation is a pivotal step in moving newly discovered biomarkers towards clinical implementation. We performed a systematic review of studies on biomarkers related to OLP, wherein biomarkers have been described in at least two independent studies. Our aim was to determine whether any of these biomarkers might be promising in predicting the increased risk of malignant transformation of OLP. We searched the following databases until August 2021: PUBMED, EMBASE, and Web of Science. Due to high heterogeneity, a qualitative rather than quantitative assessment was conducted. Only proteins that consistently showed a significantly high level of expression in neoplastic tissues versus OLP in two or more publications were considered as promising markers. Initial database researches identified 1671, of which 24 articles were included in the final analysis. The most frequently reported proteins were p53, Bcl-2 and Ki-67, though there were controversies. PCNA and P21 were the only proteins that showed consistent evidence of clinical usefulness as cancer predictors to be considered as promising markers. Extensive methodological variations in the evaluation of expressions and statistical analyses of the included markers were observed, which hampered comparisons of the results. Multiple levels of heterogeneity with a scarcity of high-quality studies were identified. PCNA and P21 were identified as promising predictive markers for evaluating the risk of malignant transformation of OLP, but they require further validation. The focus of future research on validation of predictive biomarkers of OLP should be considered as a high priority because it will accelerate the introduction of newly discovered markers into the clinical setting.