The regulation of the gene-regenerating family member 1 alpha (REG Iα) played important roles in cancer cell biology. However, the correlation between its gene product serum REG Iα and cancer has not been evaluated. In this observational study, 130 hospitalized patients from the department of internal medicine in Zhongda Hospital Southeast University were included and assigned to cancer or noncancer groups. History, clinical, and laboratory data were obtained. Serum REG Iα levels and alanine aminotransferase were found significantly higher in patients with cancer (P < .001 and P < .05 respectively). Logistic regression analysis indicated that REG Iα was an independent risk factor for cancer (P < .001). The area under the curve of REG Iα was 0.764 and the optimal cut-off point of REG Iα was 46.97 ng/mL. Besides, the cancer patients with metastasis had significantly higher serum REG Iα levels than those in nonmetastasis cancer group (P < .05). In conclusion, serum REG Iα was significantly elevated in patients with cancer, and it might be a potential biomarker in predicting cancer occurrence and development.