Objective To investigate the expression and clinicopathological significance of nuclear factor-κB (NF-κB) and epidermal growth factor receptor (EGFR) in gastric cancer tissues. Methods The expressions of NF-κB and EGFR in 106 gastric cancer patients and corresponding normal gastric mucosa tissues were compared and analyzed by immunohistochemical method. The correlation between the expression of NF-κB and EGFR in gastric cancer was analyzed, and investigate its relationship with clinical pathology characteristic. Results The results showed that the positive expression rate of NF-κB protein in gastric cancer was 67.9%, which was significantly higher than that of the corresponding normal gastric mucosa tissue (5.9%, P<0.05). The positive rates of EGFR expression in gastric cancer tissue and normal mucosal tissue were 65.1% and 2.9%, respectively. The expression of EGFR in gastric cancer tissue was significantly higher than that in normal gastric mucosa tissue (P<0.05). The expression of NF-κB in gastric cancer tissue was significantly positively correlated with the expression of EGFR (r=0.202, P=0.034). The high expression of NF-κB and EGFR in gastric cancer tissues is correlated with the depth of tumor invasion, lymph node metastasis, and clinical stage. Conclusion The high expression of NF-κB and EGFR in gastric cancer tissues was associated with cancer progression, and their expression was positively correlated, suggesting synergistic effect of NF-κB and EGFR in the development and progression of gastric cancer.