Objective To investigate the clinical prognostic value of peripheral blood albumin and fibrinogen levels in advanced non-small cell lung cancer (NSCLC). Methods A total of 158 patients with advanced NSCLC who were admitted to Chest Hospital District of the Affiliated Brain Hospital of Nanjing Medical University from May 2010 to September 2015 were retrospectively analyzed. All patients received systemic chemotherapy plus or not local radiotherapy. The clinicopathological characteristics of patients and the results of peripheral serum protein and fibrinogen were collected, and the correlation between peripheral serum protein and fibrinogen levels and prognosis was analyzed. Results The median level of serum albumin and plasma fibrinogen was 40.8 g/L (27.6-46.9 g/L) and 3.4 g (2.4-5.2 g/L), respectively, and the median serum albumin and fibrinogen ratio (AFR) was 12.1 (6.2-17.0). The median overall survival (OS) time in the increased serum albumin group (≥40 g/L) and the decreased serum albumin group (<40 g/L) was 17.0 and 9.0 months, respectively, and the median OS time in the increased plasma fibrinogen group (≥40 g/L) and the decreased plasma fibrinogen group (<40 g/L) was 9.0 and 17.0 months, respectively. The median OS time in the increased AFR group (≥10) and decreased AFR group (<10) was 17.0 and 8.0 months, respectively, and there were significant differences between two groups (all P < 0.01). Multivariate analysis showed that serum albumin level (HR = 1.58, 95% CI 1.20-2.06, P = 0.003), plasma fibrinogen level (HR = 1.43, 95% CI 1.01-2.03, P = 0.046) and AFR (HR = 1.81, 95% CI 1.22-2.62, P = 0.001) were independent prognostic factors of OS. Conclusions In patients with advanced NSCLC, higher albumin level and/or lower fibrinogen level are associated with better clinical prognosis. Peripheral serum albumin, fibrinogen level and AFR are independent prognostic factors for advanced NSCLC. Key words: Cacinoma, non-small cell lung; Albumin; Fibrinogen; Prognosis