Objective To compare the value of ultrasound and CT in the diagnosis of nodular goiter with thyroid cancer. Methods The ultrasonic and CT imaging data of 48 patients with nodular goiter complicated with thyroid cancer diagnosed by clinical pathology were analyzed retrospectively and compared with clinical pathology. Results The diagnostic accuracy of ultrasound combined with CT (89.58%) was significantly higher than that of ultrasound (60.42%) and CT (72.92%) (P<0.05). The ultrasound findings of 29 cases were abnormal, including 23 cases of nodules of which the shape was irregular and aspect ratio was larger than or equal to 1, edges were with spicule signs and there were no clear boundaries with surrounding tissues. 19 cases of nodules were with calcification, in sand granular shape. 24 cases of blood flow signal was abundant and there were 13 cases of lymph node metastasis. 35 cases of CT findings were abnormal, including 28 cases of plain CT scan showing low density, 24 cases with inversion-boundary signs, 30 cases of irregular shape, 19 cases of adjacent thyroid capsule interruption, 25 cases of nodules with calcification lesions and 11 cases with lymph node metastasis. Conclusion Ultrasound combined with CT examination can improve the diagnostic accuracy rate of nodular goiter with thyroid cancer.