Abstract: Objective To observe bcl-2 expression and its correlation with apoptosis antagonism and immune evasion of small cell lung cancer cell line and explore the application of bcl-2 antisense thio-oligonucleotide (bcl-2 SON) in gene therapy for lung cancer. Methods Western blotting was performed to detect bcl-2 expression in NCI-H69 cell line expressing Bcl-2 protein treated with bcl-2 SON. The treated NCI-H69 cells, along with the cells without bcl-2 SON treatment and NCI-H82 cells that did not express Bcl-2 protein, were respectively co-cultured with tumor-infiltrating lymphocytes (TILs) isolated from fresh tumor samples, and the apoptosis of the lung cancer cells was assessed by JAM assay. Results Western blotting revealed obvious inhibition of bcl-2 expression in NCI-H69 cells in response to bcl-2 SON treatment. JAM assay showed that the apoptosis of bcl-2 SON-treated H69 cells and NCI-H82 cells increased with the elevation of TIL ratio in the co-culture, while such changes were not observed in NCI-H69 cells without bcl-2 SON treatment. Conclusion Small cell lung cancer cells expressing bcl-2 may antagonize the antitumor immune attack in the host, and bcl-2 SON may provide an effective alternative in gene therapy for small cell lung cancer.