Upregulation of Angiotensin Converting Enzyme-2 (ACE2) was frequently observed in patients with lung cancer. Interestingly, our recent study revealed that the same ACE2 receptor was also strongly upregulated in the lungs during SARS-CoV2 infection. Therefore, it is possible that the upregulated expression of ACE2 in lung tumors might increase the susceptibility to COVID-19 infection in lung cancer patients. However, the molecular mechanism for the regulation of ACE2 is known neither in lung tumors nor in COVID-19. Under this review, we attempt to identify transcription factors (TFs) in the promoter of ACE2 that promote the expression of ACE2 both in COVID-19 infection and lung cancer. This review would decipher the molecular role of ACE2 in the upscaled fatality of lung cancer patients suffering from COVID-19.