Objective: Amongst the current detections of tumor markers, measurement of serum tumor markers is the most convenient and the safest way. However, there are few promising serum tumor markers with confirmed prognostic value in NSCLC (non-small-cell lung cancer, NSCLC). Therefore, scientists only grafted the useful tumor markers, such as CA125, CA19.9, NSE, SCC, CEA and CYFRA21.1 which have been found in other solid tumors. However, previous reports about this issue remain controversial. This study is to analyze the prognostic values of these 6 markers in stage I NSCLC. Methods: One hundred and sixty four patients with stage I NSCLC who underwent operation by single-surgery-team in Department I of Thoracic Surgery, Peking University Cancer Hospital between March 2000 and March 2011 were included. These patients had measurement of CA125, CA19.9, NSE, SCC, CEA and CYFRA21.1 using electrochemiluminescence immunoassay one week before operation. The relationship between the level of these 6 tumor markers and long term survival rate was analyzed. Results: The positive rate for CA125, CA19.9, NSE, SCC, CEA and CYFRA 21.1 in the 121 adenocarcinoma patients was 5.7%, 5.7%, 18.3%, 5.3%, 18.3%, and 20.7% respectively; whereas 3.1%, 2.6%, 23.8%, 26.8%, 14.0%, and 42.9% in 43 non-adenocarcinoma patients, respectively. In univariate analysis, the overall 5 year survival rate of patients with elevated CYFRA21.1 level was lower than that of patients with normal level in ADC subgroup (54.5% vs. 83.8%, p < 0.05) and in all 164 cases (49.5% vs. 76.4%, p < 0.05). In multivariate analysis, the level of CYFRA21.1 was an independent prognostic factor. But the other 5 markers didn’t show significant prognostic value. Conclusions: We found that the prognostic values of CA125, CA19.9, NSE, and SCC for stage I NSCLC are limited. CYFRA21.1 might be a hopeful prognostic serum tumor marker for stage I NSCLC.