BACKGROUND LncRNA CASC2 has been established to have critical functions in tumorigenesis but, while its involvement in high-glucose-induced chronic renal failure remains unclear. MATERIAL AND METHODS We included patients with type 2 diabetes combined with chronic renal failure, as well as patients with diabetic retinopathy, diabetic ketoacidosis, diabetic foot infections or diabetic cardiomyopathy, and diabetic patients without any obvious complication, as well as healthy controls. Blood samples and renal tissues were obtained from each participant and expression of lncRNA CASC2 in those tissues was detected by qRT-PCR. Diagnostic value of lncRNA CASC2 for type 2 diabetes combined with chronic renal failure was evaluated by ROC curve analysis. All patients were followed up for 5 years and the occurrence of chronic renal failure was recorded. RESULTS Compared with healthy controls, expression of lncRNA CASC2 in serum and renal tissue was specifically downregulated in patients with type 2 diabetes combined with chronic renal failure but not in type 2 diabetic patients combined with other complications. Follow-up showed that patients with low serum level of lncRNA CASC2 had significantly higher incidence of chronic renal failure. CONCLUSIONS lncRNA CASC2 is a reliable diagnostic biomarker for type 2 diabetes combined with chronic renal failure and low serum level of lncRNA CASC2 predicts the occurrence of chronic renal failure in patients with type 2 diabetes.