Resistance of cancer cells to chemotherapy and/or radiotherapy is a major challenge to current anticancer treatment. The NF-κB signaling pathway plays an important role in tumor development and progression, and results in unsatisfactory treatment outcome. Inhibition of the NF-κB signaling cascade may sensitize the resistant cancer cells to chemotherapy and/or radiotherapy. Here, the correlation of NF-κB molecules with carcinogenesis and tumor progression, along with its significance in clinical practice, is reviewed. The potential clinical application of NF-κB and its associated molecules as diagnostic and therapeutic targets is also discussed.