Objective To explore the effect of membrane surface nucleolin （NCL） on activation of epidermal growth factor receptor （EGFR） signaling. Methods Immunohistochemistry was used to identify the expressions of membrane surface NCL or EGFR in pallilary thyroid carcinoma （PTC） tissues. The level of phosphorlated EGFR in TPC-1 cells was observed by Western blot. TPC-1 cells invasion capacity was detected by Transwell assay. Results The posi-tive expression rates of membrane surface NCL and EGFR in PTC tissues were 100% （56/56） and 80.4% （45/56） respe-ctively， while the expressions of NCL and EGFR were related with lymph node metastasis （P＜0.05）. There was posi-tive correlation between the expressions of NCL and EGFR （r=0.635， P＜0.01）. Western blot showed that anti-NCL or anti-EGFR of TPC-1 cells could inhibit the expression of phosphorlation EGFR （P＜0.01）. Transwell assay showed the number of membrane-invading cells were reduced significantly in anti-NCL group anti-EGFR group （P＜0.01）. Conclusions Membrane surface NCL may be a kind of indispensable component in activation of EGFR signaling， by which EGFR can participate in growth and invasion of tumors. NCL can be used as a target for developing a new field of tumor treatment.