Arylidine constitute a new class of potential antitumor compounds. The efficacy of these potential lead molecules in the high altitude regions where natural hypoxia predominates is not known. In the current investigation, arylidine derivative MLT-40 was evaluated for a potential lead molecule against colorectal cancer cell lines HCT 116 and normal control cells CCD-80-Co in the normoxia and natural (marginal) hypoxia conditions. The results of proliferation assessment showed an average of 10-fold reduction in inhibition of HCT 116 cells with about 500 nM MLT-40 while there were no significant changes noted with marginal hypoxia conditions. Proportionate increase of the apoptotic cells and large M4 fraction of cell cycle assessment with MLT-40 concentrations from 250 and 500 nM clearly demonstrated anti-cancer activity. Bcl-2/BAX ratio below 1 showed induction of apoptosis as gross mechanism behind HCT 116 inhibition by MLT-40. Collectively these results show MLT-40 as an effective anti-colorectal cancer lead molecule irrespective of normoxia or natural hypoxia.