Objective To investigate the rationality and clinical effect of different thyroid nodules surgical treatment. Methods A total of 120 patients with thyroid nodules admitted to our hospital from January 2018 to January 2019 were randomly divided into group A and group B, respectively. Group A patients did not undergo fine needle extraction. Aspiration cytology was performed directly for thyroid nodule resection. Group B patients underwent ultrasound negative pressure guided thyroid fine needle aspiration cytology and were given surgical treatment. The changes of benign and malignant nodules before and after surgery were compared between the two groups including postoperative recurrence rate, complication rate and surgical outcome. Results The proportion of patients with residual malignant nodules in group A was higher than that in group B (P=0.001). The proportion of patients with healthy no-nodular lesions in group A was lower than that in group B (P=0.002). The recurred rate of malignant nodules in group A was higher than that of group B (P<0.05). There was no significant difference in the incidence of postoperative complications between the two groups (P>0.05). The total effective rate of group A was lower than that of group B (P<0.05). Conclusion Preoperative effective ultrasound puncture diagnosis, intraoperative ultrasound guided surgery and postoperative anticancer chemotherapy treatment may improve the efficiency of thyroid nodules in patients with thyroid nodules. Group B has important clinical value.