Plasma is defined as ionized gas containing energy particles including electrons, ions, and neutral atoms. Non-thermal plasma can be generated at a much lower temperature. Recent studies show that non-thermal plasma has been used in many ways, such as wound healing, sterilization, blood coagulation and anti-cancer effect. The differential responses of cancer cell lines after plasma treatment were studied. The effects were examined in four head and neck cancer cell lines including FaDu, SAS, CAL 27 and Detroit 562. Through MTS assay, the study showed that the percentage of viable cancer cells decreased with N2/He micro-plasma exposure time. DNA content for sub G0 population was determined using PI staining followed by flow cytometry. Plasma treatment resulted in a significant enrichment in the number of cells in the sub G0 phase, representing the apoptotic cells. In conclusion, these results suggest that N2/He micro-plasma might be a potential treatment for cancer therapy.