Although transarterial chemoembolization has improved as an interventional method for hepatocellular carcinoma, subsequent postembolization syndrome is a threat to the patients' quality of life. This study aimed to evaluate the effectiveness of a clinical decision support system in postembolization syndrome management across nurses and patient outcomes. This study is a randomized controlled trial. We included 40 RNs and 51 hospitalized patients in the study. For nurses in the experimental group, a clinical decision support system and a handbook were provided for 6 weeks, and for nurses in the control group, only a handbook was provided. Notably, the experimental group exhibited statistically significant improvements in patient-centered caring attitude, pain management barrier identification, and comfort care competence after clinical decision support system implementation. Moreover, patients' symptom interference during the experimental period significantly decreased compared with before the intervention. This study offers insights into the potential of clinical decision support system in refining nursing practices and nurturing patient well-being, presenting prospects for advancing patient-centered care and nursing competence. The clinical decision support system contents, encompassing postembolization syndrome risk prediction and care recommendations, should underscore its role in fostering a patient-centered care attitude and bolster nurses' comfort care competence.