PurposeSplenectomy is an effective treatment for correcting cytopenia caused by hypersplenism secondary to cirrhosis. However, other potential benefits have not been well characterized. In this study, we investigated the value of splenectomy as it relates to improvement in hepatic function, liver regeneration, and health-related quality of life, and their association with baseline characteristics to clarify which patients may benefit the most from splenectomy.MethodsPatients with hypersplenism secondary to cirrhosis treated by splenectomy were retrospectively reviewed. Hepatic function was reflected by hematologic indices and albumin-bilirubin score. Liver volume was measured by imaging software, and quality-of-life was assessed by a 36-question short-form questionnaire. The changes in these three aspects after splenectomy were evaluated in the whole cohort and compared between subgroups.ResultsThe hepatic function of the patients significantly improved after splenectomy, and this was reflected by elevated serum albumin, shortened prothrombin time, and decreased albumin-bilirubin score. Patients with baseline albumin-bilirubin grade 2 or 3 and age < 56 years showed significantly decreased albumin-bilirubin score after splenectomy, whereas other subgroups did not. Moreover, liver volume increased remarkably after splenectomy in patients with baseline albumin-bilirubin grade 1, but not in those with grade 2 or 3. Significant improvement in quality-of-life occurred in the entire cohort after splenectomy, but more profound improvement was found in patients with albumin-bilirubin grade 2 or 3.ConclusionsSplenectomy improves hepatic function, increases liver volume, and also improves quality-of-life in different subsets of patients with cirrhosis and hypersplenism. Baseline characteristics, such as albumin-bilirubin grade and age, are helpful in estimating the potential benefits of splenectomy for patients before surgery.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11605-023-05610-2.