Objective To explore the differential diagnosis of TI-RADS class 4 nodules based on ultrasonographic characteristics and types of focal strong echo. Methods A retrospective analysis was performed on the ultrasound data of 102 patients with TI-RADS class 4 thyroid nodules admitted to the hospital between January 2018 and December 2020. The two-dimensional ultrasound characteristics of TI-RADS class 4 nodules were analyzed. The focal strong echoes of thyroid nodules were classified. The independent risk factors to predict the malignancy of TI-RADS class 4 thyroid nodules were screened out by binary Logistics multivariate analysis. Results In the 102 patients with TI-RADS class 4 nodules, pathological diagnosis showed that there were 214 thyroid nodules, including 181 benign nodules and 33 malignant nodules. The differences in two-dimensional ultrasound signs (edge, aspect ratio, echo) between benign and malignant thyroid nodules were statistically significant (P<0.05). In malignant nodules, strong echoes of types V and VI were in the majority [12 (36.36%), 11 (33.33%)]. In benign nodules, strong echoes of types I and II were in the majority [98 (54.14%), 59 (32.60%)]. There were significant differences in strong echoes of types I, II, IV, V and VI between benign and malignant nodules (P<0.05). Binary Logistic stepwise regression analysis showed that low echo, aspect ratio ≥1 and strong echoes of types IV, V and VI were independent predictors of malignant thyroid nodules (OR=4.289, 4.051, 3.333, 4.047, 4.112, P<0.05), while strong echoes of types I and II were independent predictors of benign thyroid nodules (OR=0.291, 0.305, P<0.05). Conclusion Ultrasonographic characteristics and types of focal strong echo have certain reference value in the differential diagnosis of benign and malignant TI-RADS class 4 thyroid nodules.