Accurately defining infiltrative tumor margin is extremely crucial for complete resection and avoiding mistaken removal of normal tissue. Currently, pre-operative MRI imaging is the most widely-used strategy for defining tumor margin. However, there are plenty of insurmountable disadvantages in terms of accuracy, low resolution, mismatch and so on. This research aims to develop one targeting MRI-Raman nanoprobe able to pre-operatively and intra-operatively evaluate infiltrative margin of head and neck carcinoma (HNSCC) and real-timely guide tumor resection. The results showed that the nanoprobe greatly benefits the complete resection of HNSCC. As a result, the prognosis of tumor-bearing rabbits were considerably improved.