Purpose <p>To explore the value of ultrasound in efficacy assessment and prediction of preoperative targeted treatment for gastrointestinal stromal tumor (GIST), using pathological assessment as a reference.</p> Methods <p>A total of 35 GIST patients with preoperative targeted therapy were included in this retrospective study. The efficacy was evaluated using both ultrasound and pathology. Spearman correlation analysis and Kappa test were used to analyze the correlation and consistency between the evaluation results of ultrasound and pathology. Univariate analysis was used to obtain relevant predictive indicators of treatment response, which were then included in ordered logistic regression analysis to screen for independent predictive factors.</p> Results <p>In the 35 patients who underwent targeted therapy, the results of pathological assessment suggested complete response in one patient, high response in 11 patients, partial response in 15 patients, and no response in eight patients; the results of ultrasound assessment were complete response in zero patients, partial response in 20 patients, stable disease in nine patients, and progressive disease in six patients. Preoperative ultrasound evaluation of targeted therapy for GIST was moderately consistent and highly correlated with the results of postoperative pathological evaluation. Short-to-length diameter (S/L) ratio and tumor shape were independent predictors of treatment response.</p> Conclusion <p>Ultrasound is potentially beneficial for evaluating and predicting the response to treatment of GIST.</p>