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Background: We aimed to demonstrate the effects of tumor treating fields (TTFields) in head and neck squamous cell carcinoma (HNSCC) cells when combined with radiotherapy (RT) and chemotherapy. Methods: Two human HNSCC cell lines (Cal27, FaDu) received five different treatments: TTFields, RT +/− TTFields and RT + simultaneous cisplatin +/− TTFields. Effects were quantified using clonogenic assays and flow cytometric analyses of DAPI, caspase‐3 activation and γH2AX foci. Results: Treatment with RT + TTFields decreased the clonogenic survival as strong as treatment with RT + simultaneous cisplatin. The triple combination of RT + simultaneous cisplatin + TTFields even further decreased the clonogenic survival. Accordingly, combination of TTFields with RT or RT + simultaneous cisplatin increased cellular apoptosis and DNA double‐strand breaks. Conclusion: TTFields therapy seems a promising combination partner in the multimodal treatment of locally advanced HNSCC. It could be used to intensify chemoradiotherapy or as alternative to chemotherapy. [ABSTRACT FROM AUTHOR]