Abstract: The aim of our study is to explore the safety and efficacy of apatinib in treatment of squamous cell carcinoma. Methods: This study comprised 17 patients histologically confirmed with squamous cell carcinoma in the oncology department of Xuzhou Central Hospital from December 2015 to April 2017. Results: There were 17 patients, including 10 patients with lung cancer, 7 patients with other cancers. Sixteen patients received apatinib second-line and beyond therapy. The rate of partial response (PR), stable disease (SD), and progression disease were 46.7%, 46.7% and 6.7% for the 15 evaluated patients, respectively. There were no grade 3/4 hypertension (23.5%) and hand-foot syndrome (23.5%) occurred. Severe adverse events occurred in 3 patients.. The median PFS (mPFS) of all patients was 5.20 (95% confidence interval CI, 3.32-7.08 months) months, while the mPFS of lung caner was 6.10 (95% CI, 4.63-7.57 months) months. Conclusions: Apatinib is effective for squamous cell carcinoma. The toxicity of apatinib is acceptable.