Objective To explore the effect of transcription factor E2F1 on the apoptosis of small cell cancer line H446. Methods Plamid vector- mediated E2F1 small hairpin RNA (shRNA) was used to silence E2F1 in H446 cell. RT-PCR and western-blot assay were used to detect the expressions of E2F1 and Bcl-2. The apoptosis rate in H446 cell line was detected by flow cytometry assay. Result E2F1 protein was suppressed in shRNA1-modified H446 cell. Sgnificant difference of the apoptosis was shown between E2F1 shRNA1 group and the other two groups. Additionaly, the expression of Bcl-2 protein increased in E2F1 shRNA1-modified cell line. Conclusions E2F1 is highly expressed in H446 small cell lung cancer cell line. E2F1 promotes apoptosis of H446 through upregulating Bcl-2 expression.