Background: Oral squamous cell carcinoma (OSCC) is the sixth most human cancer with high morbidity rate. The oral cavity is considered one of ten most frequent sites of cancer internationally .OSCC occurs commonly in tongue, lip and floor of mouth. Aim: This study was designed to assess the level of matrix metalloproteinase-9 in serum and saliva in human oral squamous cell carcinoma. Design: Thirty patients were selected from the outpatient clinic of faculty of oral and dental medicine, Cairo University and National Cancer Institute. Patients included in the study were divided into two groups; Group (1): included fifteen patients diagnosed as having oral squamous cell carcinoma (patient group) and Group (2): included fifteen individuals free from any systemic disease (control group). Results: The present study showed that the level of matrix metalloproteinase-9 in serum and saliva was increased in patients with OSCC as compared to the control group (P<0.01). Although there was a negative correlation between the level of matrix metalloproteinase in serum and saliva and the grade of OSCC as well as the patient's age distribution. Conclusion: From the present study it was concluded that serum and salivary MMP-9 can be considered as a diagnostic tumor marker in patients with OSCC. MMP-9 is not a prognostic marker since its level isn't correlated to the tumor grade. Keywords: Oral squamous cell carcinoma, matrix metalloproteinase-9