Background: PD-1 inhibitors plus chemotherapy is a standard of first-line therapy in advanced lung squamous cell carcinoma (LUSC). Previous preclinical and clinical studies suggested that the combination of anti-PD-1 antibody SHR-1210 and VEGFR-2 inhibitor apatinib significantly improved anti-tumor effects. The aim of this study was to evaluate the efficacy and safety of SHR-1210 in combination with apatinib for advanced LUSC patients as a first-line treatment. Methods: In this phase II study, patients diagnosed with stage IIIB or IV advanced LUSC were enrolled. All patients received SHR-1210 (200mg q2w) and apatinib (250mg po qd) until disease progression or unacceptable toxicity. Treatment efficacy was assessed every 3 cycles (6 weeks). The primary endpoint is progression-free survival (PFS). Secondary endpoints are objective response rate (ORR), disease control rate (DCR), and overall survival (OS), which according to RECIST 1.1. Results: At the primary analysis (data cutoff Feb 10, 2020), 26 advanced LUSC patients had enrolled, and 17 patients of which were evaluable. Baseline characteristics were shown that median age was 67 years, male percentage was 92.3% (24/26), and clinical stage IV percentage was for 57.7% (15/26). The median follow-up time was 3.1 months (range 0.4-13.7 months) in all included patients. No complete response (CR) was reported. Partial response (PR) was achieved in 13 (76.5%) and stable disease (SD) in 4 (23.5%). The ORR and DCR in 17 evaluable patients were 76.5% and 100%, respectively. The most common treatment-related adverse events were hypertension (42.3%), rash (38.5%), hand-foot skin reaction (26.9%), and reactive cutaneous capillary endothelial proliferation (RCCEP) (15.4%). Of 26 patients, 5 experienced a grade ≥3 treatment-related adverse events, including one interstitial pneumonia, one hypertension, one thrombocytopenia, one RCCEP, and one aminotransferase elevation. Three patients (3/26) were reported dead, of which one died due to interstitial pneumonia and the others died of tumor progression. Twelve patients (46.2%) ever suspended treatment or adjusted the dosage of apatinib due to interstitial pneumonia, pyelonephritis, rash, thrombocytopenia, or aminotransferase elevation. Conclusions: The combination of SHR-1210 and apatinib for advanced LUSC patients was well tolerated and effective. This treatment may be a promising method for advanced LUSC as a first-line treatment. Fund Project (No: 2017FC-CXYY-3007) & Project (No: 2017MBD-013). Clinical trial information: ChiCTR1800019329.