Aims: To compare fine-needle aspiration cytology (FNAC) with imprinted gene detection in the differential diagnosis of benign and malignant thyroid nodules.Methods: A total of 34 patients (35 cases of thyroid nodules) were examined using fine-needle puncture biopsy under ultrasound guidance, and the biopsy tissues were examined by cytologic examination and imprinted gene detection. Combined with postoperative pathology and follow-up results, the diagnostic value and consistency of the two methods were analyzed and compared.Results: The detection of benign and malignant thyroid nodules by ARHI imprinted gene had a high consistency with FNAC, and ARHI imprinted gene detection had a higher detection rate, sensitivity, and accuracy.Conclusions: Imprinted gene detection has high accuracy and sensitivity in the differential diagnosis of benign and malignant thyroid nodules. It provides a scientific reference for clinical treatment and should be incorporated into diagnostic protocols for thyroid tumor.