Objective: In this study, the expression of several lymphangiogenic growth factors was investigated to determine the mechanism underlying lymphangiogenesis in oral squamous cell carcinoma (OSCCa). Materials and Methods: An immunohistochemical study was performed to determine the lymphatic microvessel density (LMVD) and the expression of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), basic fibroblast growth factor ( bFGF), insulin-like growth factors (IGF-I/II), and hepatocyte growth factor (HGF) in 25 OSCCa and 20 normal oral mucosal tissue samples. Results: Significantly higher levels of expression of VEGF, PDGF, bFGF, HGF, IGF-I, and IGF-II existed in OSCCa tissue compared to normal oral mucosal tissue (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, and p < 0.01, respectively; Mann-Whitney test). In OSCCa samples, significant positive correlations, based on the Spearman correlation test, existed between the LMVD and VEGF (r = 0.573; p < 0.01), PDGF (r = 0.559; p < 0.01), bFGF (r = 0.516; p < 0.01), HGF (r = 0.448; p < 0.05), and IGF-I (r = 0.6; p < 0.01), but no correlation existed between LMVD and IGF-II (r = 0.380; p > 0.05). Conclusion: These findings indicate that several.