Midkine, a new member of the heparin-binding growth factor family, was found recently to have a high expression level in many carcinoma specimens, including oesophagus, gall, bladder, pancreas, colorectum, breast and lung carcinomas, but few relevant studies have been performed. The aim of this study was to investigate the expression of midkine in oral squamous cell carcinoma (OSCC) and its correlation with tumour angiogenesis. Surgical specimens from 62 cases of OSCC and 10 cases of normal oral mucosa were examined by immunohistochemistry. The relationship between expression of midkine and the clinicopathological data and tumour angiogenesis was analysed. Midkine proteins were overexpressed in OSCC. The level of midkine expression was found to be significantly correlated with tumour size (P = 0.01), clinical stage (P = 0.002) and prognosis (P = 0.038). High midkine expression was associated with higher tumour angiogenesis as reflected by increased vascular endothelial growth factor expression (P = 0.005) and higher microvessel density (P = 0.004). These results indicate that midkine may be of great value in assessing the development and prognosis of OSCC, and could be taken as a new target for OSCC therapy.