Background: DNA damage-inducible 1 (Ddi1), one of the ubiquitin-like and ubiquitin-associated family of proteins, may function in the regulation of the ubiquitin-proteasome pathway, which has been validated as a target for antineoplastic therapy. We investigated Ddi1 expression in human lung cancer tissues and evaluated the relationship of this expression pattern with clinicopathological factors in patients with non-small-cell lung cancer (NSCLC). Methods: Ddi1 expression was examined by immunohistochemistry in tumor tissues from 97 patients with stage I NSCLC, who had undergone curative surgical resection at two tertiary referral hospitals from 1993~2004. None of the patients received preoperative chemotherapy and/or radiation therapy. Results: Thirty-nine (40.2%) of the 97 cases were positive for Ddi1. Ddi1 expression was dominantly seen in cytoplasm rather than in the nuclei of cancer cells in all histological types, whereas adjacent nontumoral lung tissue showed negative Ddi1 staining in most cases. Ddi1 expression tended to increase in well-differentiated tumors but without statistical significance. Positive Ddi1 expression was associated with a tendency for better disease-free survival and disease-specific survival, although the difference was not significant. Conclusion: Ddi1 expression is a property of NSCLC. Because Ddi1 could be a potential target for cancer therapy, more research is needed to evaluate its role in NSCLC.