To analyze the effect of real-time shear wave elastography (SWE) optimized by mathematical algorithms combined with thyroglobulin antibodies (TGAb) on the clinical diagnosis of differentiated thyroid carcinoma (DTC), a hybrid displacement estimation algorithm based on weighted phase separation and two-dimensional cross correlation was proposed. 102 patients with DTC were divided into a test group (TGAb-positive) and a control group (TGAb-negative). Real-time SWE based on hybrid displacement estimation algorithm was performed. Receiver operating characteristic (ROC) curve was adopted to analyze the characteristics of real-time SWE and its combination with TGAb to detect the sensitivity, specificity, and area under the curve (AUC) of the malignant degree of thyroid cancer. The results showed that the preoperative thyroid-stimulating hormone (TSH), thyroglobulin autoantibodies (TGAb), and thyroid peroxidase antibody (TPOAb) of TGAb-positive patients were higher than those of the TGAb-negative group ( P < 0.05 ). The preoperative tumors of TGAb-positive patients were multifocal, and the tumor size was larger than that of the TGAb-negative patients ( P < 0.05 ). The maximum Young’s modulus Emax of TGAb-positive patients was greater than that of TGAb-negative group ( P < 0.05 ). In addition, there was a very significant positive correlation between the patient’s TGAb level and Emax of Young’s modulus ( P < 0.001 ). The sensitivity, specificity, and AUC of the joint detection of real-time SWE Emax and TGAb for the malignant degree of thyroid cancer were significantly greater than those of the single real-time SWE and TGAb, and the difference was substantial ( P < 0.05 ). In short, joint detection of real-time SWE based on hybrid displacement estimation algorithm combined with TGAb had high sensitivity, specificity, and AUC for the diagnosis of DTC, which was suitable for clinical application.