Objective To introduce the hydro-dissection technique and its application in ultrasound-guided percutaneous thermal ablation therapy of neck nodular lesions. Methods A total of 1 126 patients suffering from neck nodular diseases received percutaneous thermal therapy using radiofrequency ablation or microwave ablation from May 2005 to April 2013. As a part of the treatment procedure, ultrasound-guided injection of separating liquid was performed into between the target nodules and surrounding structures to form a separating zone prior to ablation. The roles of hydro-dissection technique in improving the safety of puncture route, reducing the thermal injury to normal tissues, and enhancing the curative effects of ablation were analyzed. Results Hydro-dissection technique was successfully performed in as many as fourteen parts related to the thyroids, parathyroids, submandibular glands and lymph nodes. The key points and ultrasonic characteristics of this maneuver were well established and understood. Compared with those not receiving the technique, those receiving the technique had significantly reduced heat damage to lesion-adjacent structures (0.7% vs 15%, P<0.01) and decreased incomplete ablation rate of the first try (0.29% vs 7.4%, P<0.01). Conclusion Hydro-dissection technique under ultrasound-guidance is easy to perform, has good repeatability and reliable effect; it may serve as a safe and effective supplementary measure for thermal ablation of various neck nodular lesions.