Malignant tumors of head and neck carcinomas are the sixth most common type of cancer. Current systemic therapies for cancer show side effects in normal tissues and short-term efficacy due to drug resistance. Consequently, there is much interest in identifying new drugs for cancer treatment. Crocin (an active ingredient of saffron) has been shown to have cytotoxic effects on cancer cell lines. Chemo radiotherapy is the standard treatment for head and neck cancer. In the present study, the cytotoxic effects, inducing apoptosis and the radiation sensitivity of crocin were evaluated in the head and neck cancer cell line (HN-5). HN-5 cells were cultured in a DMEM medium and incubated with different concentrations of crocin (12.5-1000 mu g/ mL). They were exposed to 2 Gy gamma-rays. Cell viability was quantified by the MTT assay. Apoptotic cells were determined using PI staining of DNA fragmentation by flowcytometry (sub-G1 peak). Crocin decreased cell viability in HN-5 cells in a time and concentration dependent manner. Crocin also induced a sub-G1 peak in the flowcytometery histogram of treated cells compared with the control, suggesting that apoptotic cell death is caused by its toxicity. Crocin was also shown to sensitize cells to radiation-induced toxicity and apoptosis. The simultaneous use of crocin and radiation therefore increases radiation sensitivity and cell death. Thus, after further study crocin can be considered as a potential drug and sensitizer in cancer treatment.