Background: Research has shown that nursing interventions are able to affect short-term outcomes in patients with injury. However, evidence based on a comprehensive nurse-led intervention may be beneficial for trauma care. Purpose: This study was designed to assess the effect of a nursing intervention on the illness perceptions and quality of life of patients with injury. Methods: A two-group experimental design and a follow-up period of 12 months were used. Ninety-four patients were randomly assigned to either the experimental group or the control group. A nurse-led cognitive behavioral therapy intervention was used to improve outcomes. Results: The illness perception variables of “personal control” and “treatment control” were found to be significantly improved in the experimental group at 3 months after discharge, whereas “emotional perception” was significantly improved at 6 months after discharge. The intervention was also shown to improve “social quality of life” at 6 and 12months after injury. Conclusions: This study adds new knowledge related to nursing interventions for patients with injury in terms of the intervention achieving longer-term effects than the interventions examined in previous studies. The results highlight the importance of providing interprofessional collaborative care. However, the intervention protocol should be tested further in future studies.