To investigate the effect of nimotuzumab (N) combined with nab-paclitaxel, cisplatin, and fluorouracil (APF) neoadjuvant chemotherapy on the surgical margin.55 patients were divided into three groups: neoadjuvant chemotherapy and surgery group (G1, 15 cases), chemotherapy and surgery group (G2 group, 20 cases), and surgery group (G3 group, 20 cases). Tissue samples of the tumor core zone (P0), adjacent (P1, 3-5mm from tumor), distal adjacent (P2, 7-10mm from tumor), and surgical margin (P3, 15mm from tumor) were collected. Morphological changes and pathological remission rates were observed. Immunohistochemistry was used to detect the expression of EGFR, elF4E, P53, and VEGF in each specimen by statistical analysis.In the G1 and G2 groups, various degrees of degeneration and necrosis were observed in the tumor retraction area. Nine cases of MPR (major pathologic response) and 4 cases of pCR (pathologic complete response) in the G1 group; 8 cases of MPR and 3 cases of pCR in the G2 group. The expressions of p53, eIF4E, and EGFR in the samples of the three groups decreased from P0 to P2 with statistical differences (p<0.05). In the molecular tumor shrinkage area, the expression levels of p53, eIF4E, and EGFR in the shrinkage zone were lower than those in the negative margin.In summary, although there is no significant statistical difference between neoadjuvant chemotherapy with nimotuzumab combined with APF and APF alone in the pathological remission rate of locally advanced oral squamous cell carcinoma, there is a trend indicating that nimotuzumab combined with APF is superior.Copyright © 2024, the Chinese Medical Association.