Background: The introduction of anti-PD-1 antibody has greatly improved the clinical outcomes of patients with lung cancer. Pre-treatment biomarkers in peripheral blood such as neutrophil-lymphocyte ratio, cytokine level, or clinical features such as BMI, lactate dehydrogenase, and prognostic nutrition index have been shown to be predictive markers treated by immunotherapy. Here we retrospectively analyzed the efficacy of PD-1 antibody-based therapy in patients with locally advanced un-operable or metastatic lung cancer patients and report an association between peripheral blood biomarkers with clinical response in these patients. Methods: We conducted a single-center study by including medical record data for lung cancer patients treated with PD-1 antibody first-line or posterior-line either as monotherapy or in combination with chemotherapy. The patients enrolled from March 2020 to December 2021 were treated with albumin paclitaxel or pemetrexed plus carboplatin、lobaplatin or cisplatin combined with PD-1 antibody. The clinical response were assessed after 2 circles of therapy. Peripheral blood were drawn prior to therapy and post therapy. Multiple Th1 and Th2 cytokines levels in the blood serum were evaluated and phenotype of T cells of peripheral blood were also analyzed. The association between cytokines levels, T cells phenotype and clinical response were investigated. Results: 61 patients with stage IIIA-IV lung cancer were enrolled in the study. 40 non-squamous NSCLC patients, 15 Squamous NSCLC patients and 6 SCLC patients received PD-1 antibody with chemotherapy. 40(65.6%)patients were first-line therapy and 21(34.4%) were posterior-line treatment. 42(68.9%) patients achieved partial response(PR), 7 (11.5%) patients were stable(SD) and 12(19.6%) patients had progressed disease (PD). The disease control rare(DCR) was 80.4%. In DCR group, higher levels of IFN-γ(P = 0.023,P < 0.05), TNF-α(P = 0.007,P < 0.05)and IL-5 (P = 0.002, P < 0.005) were detected in peripheral blood prior to the treatment comparing to PD group. Besides, the reduction of lymphocyte absolute counts in peripheral blood after PD-1 antibody-based therapy was associated with disease progression(P = 0.023,P < 0.05). Furthermore, higher CD8⁺CD27⁺T cells in peripheral blood before therapy was associated with worse clinical response(P = 0.019,P < 0.05) and higher ratio of CD4⁺CD45RO⁺CD62L⁺/ CD4⁺CD45RO⁺CD62L^-seems to related with better clinical response, though without statistic difference due to limited sample size. Conclusions: These results suggest for the first time that serum IFN-γ, TNF-α and IL-5 levels could predict clinical efficacy with anti-PD-1 blockade therapy in lung cancer patients. Other biomarkers include lymphocyte counts or phenotype may also have predictive value. Large prospective studies need to further clarify the value of these biomarkers.