Objective To investigated the effect of rs79077373 (C/T) mutation in promoter region of CD59 on CD59 transcription activity. Methods Bioinformatic analysis was performed to predict potential mutation in transcription factor binding site of the promoter region of CD59 that may affect transcription activity. Two different pGL3-CD59 promoter luciferase reporter constructs, CD59 rs790773737 T and pGL3-rs79077373C, were generated. Constructers were co-transfected with pRL-SV40 plasmid into A549, NCI-H2030 and NCI-H23 cells for manifestation of the transcription activity of CD59. Results Bioinformatic analysis unveiled that alteration of CD59 rs79077373 T allele to C allele may affect the transcription activity. The reporter gene expression suggested a 2.00- fold, 1.82-fold and 1.42-fold increase of transcription activity in A549, NCI-H2030 and NCI-H23 cells in CD59 rs79077373 T allele group compared with CD59 rs79077373C group (respectively, P < 0.05). Conclusions CD59 rs79077373 carrying the T allele enhances CD59 transcriptional activity.