This study was aimed to explore the application value of ultrasound-guided peripherally inserted central catheter (PICC) combined with predictive nursing in the treatment of large-area severe burns. 88 patients with large-area severe burns who visited hospital were chosen as the research objects. They were randomly divided into the observation group and the control group, with 44 cases in each. The patients in the observation group were treated with ultrasound-guided PICC combined with predictive nursing, while those in the control group were treated with traditional PICC and nursing methods. Then, the anxiety of patients was compared between groups by the Self-rating Anxiety Scale (SAS), while the depression was compared by the Self-rating Depression Scale (SDS). The pain of the patients was analyzed by the McGill Pain Questionnaire (MPQ), and a self-made nursing satisfaction questionnaire was adopted to evaluate the nursing satisfaction. The surgery-related indicators of the patients were detected and recorded (the success rate of one-time puncture, the success rate of one-time catheter placement, incidence of complications, heart rate, blood pressure, etc.). The success rates of one-time puncture (93% vs. 86%) and of catheter placement (95% vs. 81%) in the observation group were significantly higher than those in the control group, P < 0.05 . The pain scores of the observation group were much lower than those of the control group at each time period, P < 0.05 . The number of patients with negative emotions such as anxiety and depression in the observation group was markedly less than that in the control group. The incidence of complications in the observation group was notably lower than that in the control group (4.5% vs 18%), P < 0.05 . The nursing satisfaction of the observation group was significantly higher than that of the control group (93% vs 79.5%), P < 0.05 . In conclusion, ultrasound-guided PICC and predictive nursing had high clinical application values in the treatment of patients with large-area severe burns.