Abstract: Objective:To detect giant cancer cells in human oral squamous cell carcinoma (OSCC) and elucidate their correlation with OSCC clinicopathological characteristics.Methods:Tumor paraffin sections and clinicopathological information of 76OSCC cases were collected from Tianjin Medical University Cancer Institute and Hospital. Morphological differences between giant cancer cells and nor -mal-sized cancer cells were observed under H&E staining and Ki 67immunohistochemistry staining, respectively. The number of giant cancer cells was counted under a microscope (× 400 ). The association between the number of giant cancer cells and the biological be -havior of OSCC was analyzed.Results:Giant cancer cells were observed in OSCC tissues, and these cells were positive for Ki-67stain -ing. The number of giant cancer cells was closely associated with clinical stage ( P=0. 02), histological grade ( P<0. 01), chemotherapy (P= 0. 01), and local recurrence ( P=0. 02). By contrast, the number of giant cancer cells was not associated with sex, age, and lymphatic and distant metastases in OSCC ( P>0. 05). Patients with more than 3/HP giant cancer cells retained poor prognosis (P<0. 05). Conclusion: Gi -ant cancer cells may play an important role in the progression, chemotherapeutic resistance, and prognosis of OSCC.