Abstract: Objective To establish an auxiliary diagnosis model for differentiate diagnosis of benign and malignant thyroid nodules with a great quantity of clinical case validation. Methods The serum samples of inpatients with thyroid nodules before surgery were collected for biochemistry, thyroid hormones and blood cells testing and case history were used for retrospective analysis to determine the correlation between clinical blood, ultrasound and clinicopathologic analysis results. Results Index of Age, TSH, HDL, N and Ult were selected in Logistic regression equation establishment. The ROC area under curve of model team was 0.882, and the ROC area under curve of validation team was 0.812. Conclusion The model established in this study has been preliminary applied the blood tests for differentiate diagnosis of benign and malignant thyroid nodules before surgery. It could provide objective guidance for surgery combined with ultrasonic examination.