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PURPOSE: To detect the expression of NF-κB and HPA in oral squamous cell carcinoma (OSCC) by tissue microarray assay and investigate their clinical significance. METHODS: Tissue microarray assay and immunohistochemistry were applied to detect the expression of NF-κB and HPA in 146 cases of OSCC and 48 cases of normal control. Chi-square test and Spearman rank correlation were performed using SPSS 13.0 software package for statistics. RESULTS: The positive rates of NF-κB and HPA were 69.2% and 63.7%, respectively. There was significant difference compared with normal oral mucosa (P<0.05). The expression of NF-κB and HPA in OSCC was significantly correlated with histological differentiation, clinical stage and lymph node or distant metastasis (P<0.05), but not with sex and age of the patients or site of the tumor (P>0.05). The expression of NF-κB had a significant positive correlation with the expression of HPA in OSCC (r=0.7301, P<0.05). CONCLUSION: The expression of NF-κB and HPA may have synergistic effect on the carcinogenesis and progression of OSCC. [ABSTRACT FROM AUTHOR]