In the present study, we found that the serum sPD‐L1 concentration was weakly correlated in a linear manner with PD‐L1 expression on tumor cells and that a high serum sPD‐L1 level was a negative predictor of disease control using anti‐PD‐1 antibody (pembrolizumab or nivolumab) and an independent negative predictor of prognosis in advanced NSCLC patients receiving anti‐PD‐1 antibody (pembrolizumab or nivolumab). This evidence concerns the gene SPDL1 and non-small cell lung carcinoma.