Lung cancer is the leading cause of cancer-related death. Many patients with lung cancer are in the advanced stages of the disease at the time of diagnosis. The 5-year survival rate for lung cancer was 10-20%, and the prognosis of lung cancer is still poor. The cross-linked N-terminal telopeptide of type I collagen (NTx) is a metabolite of type I collagen, the main constituent of the bone matrix. We measured serum NTx who underwent staging during hospitalization for initial treatment of lung cancer in our department. Then, we examined whether serum NTx would be relevant to the prognosis of non-small-cell lung cancer. This study included 176 lung cancer patients (125 males and 51 females), including 109 adenocarcinoma, 53 squamous cell carcinoma, 6 large cell carcinoma, and 8 other cancer types). Univariate and multivaliate analysis with the Cox proportional hazards model revealed that a particularly close association was found between gender, PS, disease stage, and serum NTx level and OS. Especially, a median OS of 368 days was observed for patients with a serum NTx level of <22 nmol BCE/L, which was significantly longer than the 197 days observed for patients with a serum NTx level of >22 nmol BCE/L (hazard ratio, 2.02; 95% confidence interval, 1.36–2.99; Log-rank P = 0.00037). We have thus revealed that a high serum NTx level (>22 nmol BCE/L) appears to be a risk factor for a reduction in OS in patients with NSCLC.