Introduction: Due to the increasing prevalence and high mortality rate of oral squamous cell carcinoma (OSCC) and problems with its routine treatments, more recent modalities like photodynamic therapy (PDT) have been developed. PDT effectively destroys tumor cells with minimum side effects. Research on in vitro effects of PDT may be helpful in determining the molecular mechanisms responsible for its effectiveness and can lead to the development of more efficient techniques. The aim of this study was to review the use of PDT in OSCC among in vitro studies. Methods: A literature search for English articles on PDT in OSCC was performed in PubMed, Scopus, Google Scholar, and Web of Science. Data were extracted based on the inclusion/exclusion criteria, which were detailed using the PICO framework: all eligible in vitro studies evaluating the effects of PDT on the viability of OSCC compared to controls without PDT were included. Results: Forty-one out of 567 studies were selected. The tongue was the most common OSCC site, 5-aminolevulinic acid was the most used photosensitizer (PS), cell viability/toxicity and apoptosis were the most evaluated outcomes, and lasers with wavelengths of 600-700 nm were the most common light sources and wavelengths respectively. Conclusion: PDT showed promising effects on reducing the viability of OSCC cells. Cell lines from various sources or even those originating from the same location sometimes responded differently to the same protocol. Considering the favorable results obtained from natural PSs and regarding their additional health-promoting properties, their use in future investigations with different cell lines and light specifications is recommended.