Coronavirus disease-2019 (COVID-19) is a recent world pandemic disease that is caused by a newly discovered strain of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS- CoV-2). Patients with comorbidities are most vulnerable to this disease. Therefore, cancer patients are reported to be more susceptible to COVID-19 infection, particularly lung cancer patients. To evaluate the probable reasons behind the excessive susceptibility and fatality of lung cancer patients to COVID-19 infection, we targeted the two most crucial agents, Angiotensin-converting enzyme 2 (ACE2) and C-X-C motif 10 (CXCL10). ACE2 is a receptor protein that plays a vital role in the entry of SARS-CoV-2 into the host cell and CXCL10 is a cytokine mainly responsible for the lung cell damage involving in a cytokine storm. By using the UALCAN and GEPIA2 databases, we observed that ACE2 and CXCL10 are mostly overexpressed in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). We then identified the functional significance of ACE2 and CXCL10 in lung cancer development by determining the genetic alteration frequency in their amino acid sequences using the cBioPortal web portal. Lastly, we did the pathological assessment of targeted genes using the PANTHER database. Here, we found that ACE2 and CXCL10 along with their commonly co-expressed genes are involved respectively in the binding activity and immune responses in case of lung cancer and COVID-19 infection. Finally, based on this systemic analysis, we concluded that ACE2 and CXCL10 are two possible biomarkers responsible for the higher susceptibility and fatality of lung cancer patients towards the COVID-19.