Objective: Hypersplenism is a common disease. The conventional treatment is splenectomy and partial splenic embolization; however, both of them have high complication rates and technical defects. Therefore, safer and more effective techniques should be considered for the treatment of hypersplenism. High-intensity focused ultrasound (HIFU) may provide an effective and safe way for treatment of hypersplenism. Therefore, we conducted this study to assess the safety and efficacy of HIFU in treatment of secondary hypersplenism. Methods: A total of 28 patients who suffered from secondary hypersplenism were treated with HIFU ablation. All patients who underwent HIFU were closely followedup over a year. MRI scan was performed, and the spleens were observed. Blood counts and liver function tests were also carried out.Results: In the follow-up process, the levels of white blood cells and platelets in the blood after HIFU were significantly higher than those before HIFU, liver function also improved after HIFU treatment. In addition, the symptoms were ameliorated significantly or even disappeared. The MRI showed that the ablation area had turned into a non-perfused volume, and after 12 months of HIFU ablation, the ablated area shrank evidently; the sunken spleen formed a lobulated shape and the splenic volume decreased. Conclusion: HIFU ablation is a safe, effective and noninvasive approach for secondary hypersplenism. Advances in knowledge: For the first time we used HIFU ablation to treat secondary hypersplenism. It not only expands indications of HIFU but also provides better choice for the treatment of secondary hypersplenism.Hypersplenism is a common manifestation in cirrhotic patients with portal hypertension. Liangpunsakul et al 1 reported that 70-80% of cirrhotic patients with portal hypertension have different degrees of splenomegaly and hypersplenism. Hypersplenism is a clinical syndrome characterized by splenomegaly, a variable combination of anaemia, leucopenia and/or thrombocytopaenia, compensatory bone marrow hyperplasia, reduced immunity and improvement after splenectomy. 1 The conventional treatment for patients with hypersplenism is splenectomy. However, after the first report of overwhelming post-splenectomy infection, clinical practitioners started realizing the important immunological function of the spleen. What is more, splenectomy is associated with increased risk of splenic vein thrombosis, secondary thrombocythemia and infection, particularly with encapsulated micro-organisms. 2 Several studies have shown that the spleen is an organ with a variety of important functions such as anti-infection and antitumour immunity. Therefore, it is important to retain the splenic function as much as possible when using splenomegaly treatment. Recently, partial splenic embolization (PSE) has been used in the treatment of splenomegaly and hypersplenism, but it has high incidence of complications. Local ablation therapies, such as radiofrequency ablation (RFA) and microwave ablation, also have marked improvement for...