Cutaneous squamous cell carcinoma (CSCC), the main type of non-melanoma skin cancer (NMSC), contributes to 20-30% of the overall number of NMSC cases. Some CSCCs are observed to have metastatic potential induced by solar ultra violet (UV) radiation. Celecoxib, a nonsteroidal anti-inflammatory drug, has been largely associated with prevention of many cancer types. However, the relationship between celecoxib and CSCC cell migration has yet to be determined.To determine the association between celecoxib and CSCC, we performed a series of studies in human samples and in vitro models to assess the influence of celecoxib in CSCC cell migration.In the present study, we found that celecoxib suppresses CSCC cell migration via inhibition of SDF1-induced endocytosis of CXCR4. In addition, ERK/AKT signaling pathways were found to play a key role in this biological process.Our study provides promising evidence that celecoxib could serve as a potential preventative agent for the metastasis of CSCC cells.