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Background/Aims: Nasopharyngeal carcinoma is a common head and neck cancer in South China and Southeast Asia. Radiotherapy is the standard treatment for nasopharyngeal carcinoma. Accumulating evidence showed that the expression of miR-34a was abnormal in nasopharyngeal carcinoma. Here, this study investigates the effect of miR-34a on radiosensitivity of nasopharyngeal carcinoma cells and explored the underlying mechanisms. Methods: Reverse transcription quantitative polymerase chain reaction was used to analyze the expression of miR-34a in nasopharyngeal carcinoma cell lines and NP69 cells. The effect of miR-34a on radiosensitivity of nasopharyngeal carcinoma (CNE-1 cells) was evaluated by Cell Counting Kit-8, flow cytometry, and Transwell migration assays following transfection with miR-34a mimic. Luciferase reporter assay was used to assess the target genes of miR-34a. Results: In this study, it revealed that miR-34a was downregulated, while silent information regulator 1 was upregulated in nasopharyngeal carcinoma cell lines. The overexpression of miR-34a enhanced radiation-induced proliferation and migration inhibition and apoptosis in CNE-1 cells. Bioinformatics, Luciferase reporter, reverse transcription quantitative polymerase chain reaction, and Western blotting assays indicated that silent information regulator 1 is a direct target of miR-34a in nasopharyngeal carcinoma cells. Knockdown of silent information regulator 1 enhanced radiosensitivity of nasopharyngeal carcinoma cells as evidenced by increasing proliferation and migration inhibition and apoptosis after radiation exposure. Conclusion: In summary, our results indicated that the overexpression of miR-34a enhanced radiosensitivity of nasopharyngeal carcinoma cells by targeting silent information regulator 1. Further studies are warranted to investigate the potential use of miR-34a in the clinical management and treatment prediction of patients with nasopharyngeal carcinoma.