To determine whether serum levels of KLK5 and L1CAM potentially serve as biomarkers for anlotinib-responsive stratification in NSCLC patients at 3rd line, we detected the serum KLK5 and L1CAM levels at baseline in 28 refractory advanced NSCLC patients enrolled in an anlotinib clinical trial (NCT02388919), and then performed response analyses. Here, KLK5 is linked to non-small cell lung carcinoma.