Through comprehensive bioinformatics analysis, IHC and serological assessments on patients with NSCLCs, we confirmed that serum levels of sICOS can be used for early diagnosis, combined sPD-L1 and sICOS diagnosis improves efficacy and accuracy of disease diagnosis, ICOS is a potential biomarker and therapeutic target associated with the infiltration of TIICs and prognosis in patients with NSCLC. Here, ICOS is linked to non-small cell lung carcinoma.