Purpose: This study was done to confirm the role of NF-κB in cisplatin-induced apoptosis of oral squamous cell carcinoma. Materials and Methods: Five cell lines originated from different oral cancer patients were tested for the apoptosis by the treatment of cisplatin. These cells showed different degree of cisplatin-resistance and the order is OSCC-2> OSCC-3> OSCC-5> OSCC-1> OSCC-4. OSCC-2 and OSCC-4 cells were assayed for the apoptosis by measuring DNA fragmentation and TUNEL staining after cisplatin treatment. While OSCC-4 cells showed apoptosis, OSCC-2 cells showed no or very slight apoptosis by cisplatin treatment. Next, It was determined whether NF-κB activation is required in mediating cisplatin-induced apoptosis of OSCC-4. Result: The result was that elevated NF-κB activity mediated cisplatin-induced apoptosis. Conclusion: In conclusion, these findings suggest that NF-κB activation is essential to cisplatin-induced apoptosis and it may be involved in cisplatin resistance in OSCC cells.