Insulin-like growth factor-binding protein-2 (IGFBP-2) is considered to be a human tumor antigen, and the tumor-specific immunity of IGFBP-2 has been reported in several types of cancer. The purpose of this study was to evaluate whether autoantibodies to IGFBP-2 can be used as diagnostic markers in lung cancer. The results demonstrated that serum anti-IGFBP-2 autoantibody levels were significantly elevated in lung cancer (mean, 1,633.318 ng/ml; median, 1,651.462 ng/ml; range, 342.732-4932.582 ng/ml) compared with benign lung disease (1,210.139, 1,035.900, 547.596‑2,331.167 ng/ml) and normal controls (1,303.369, 1,194.800, 528.200-2140.500 ng/ml). The sensitivity and specificity of anti-IGFBP-2 autoantibodies in diagnosing lung cancer was 73.2 and 60.6%, respectively. When serum IGFBP-2 and anti-IGFBP-2 autoantibody were used together in the diagnosis of lung cancer, it can increase the discriminative power for lung cancer with a sensitivity of 85.7% and a specificity of 57.5%. In conclusion, this study demonstrates that circulating anti-IGFBP-2 autoantibodies can be used as a potential biomarker in diagnosing lung cancer.