The aim of this study was to explore the osteopontin expression and microvascular density in thyroid cancer, compare computed tomography (CT) and ultrasound in diagnosis of thyroid cancer and investigate the correlations of CT Features and thyroid cancer. A total of 80 patients with thyroid masses admitted to our hospital from April 2017 to August 2019 were selected, of which there were 40 with benign tumor and 40 with malignant tumor. All patients with thyroid cancer confirmed by pathological tissue biopsy were examined by ultrasound (ultrasound group) and CT (CT group). The expression of osteopontin was detected by PCR while microvascular density was tested by immunohistochemistry. Then univariate analysis and multivariate logistic regression analysis of risk factors were carried out for CT imaging diagnosis of thyroid cancer. The levels of osteopontin and microvascular density in malignant group were significantly higher than those in benign group. The incidence rates of unclear boundary and peripheral lymph node enlargement in CT group were remarkably higher than those in ultrasound group. The diagnostic rate of masses ≥1 cm in diameter was notably higher than that of masses <1 cm in diameter in thyroid cancer patients in CT group and ultrasound group (P<0.05). In addition, the diagnostic rates of follicular carcinoma and papillary carcinoma were higher, whereas those of medullary carcinoma and undifferentiated carcinoma were lower in CT group and ultrasound group. There was no significant difference in the accuracy of thyroid cancer diagnosis between CT group and ultrasound group. Moreover, diameter ≥1 cm, irregular shape, unclear boundary, calcified foci, uneven density/echo and peripheral lymph node enlargement were related risk factors for the CT imaging diagnosis of thyroid cancer, in which irregular shape, unclear boundary, calcified foci and uneven density/echo were independent risk factors for the CT imaging diagnosis of thyroid cancer. The levels of osteopontin and microvascular density were increased in thyroid cancer. CT examination may be of higher diagnostic value in diagnosis of thyroid cancer compared with ultrasound. Irregular shape, unclear boundary, calcified foci and uneven density/echo were independent risk factors for the CT imaging diagnosis of thyroid cancer.