Comorbidities such as hypertension could exacerbate symptoms of coronaviral disease 2019 (COVID)-19 infection. Patients with hypertension may receive both anti-COVID-19 and antihypertension therapies when infected with COVID-19. However, it is not clear how different classes of anti-hypertension drugs impact the outcome of COVID-19 treatment. Herein, we explore the association between the inpatient use of different classes of anti-hypertension drugs and mortality among patients with hypertension hospitalized with COVID-19. We totally collected data from 278 patients with hypertension diagnosed with COVID-19 admitted to hospitals in Wuhan from February 1 to April 1, 2020. A retrospective study was conducted and single-cell RNA-sequencing (RNA-Seq) analysis of treatment-related genes was performed. The results showed that Angiotensin II receptor blocker (ARB) and calcium channel blocker (CCB) drugs significantly increased the survival rate but the use of angiotensin-converting enzyme inhibitor/β-block/diuretic drugs did not affect the mortality caused by COVID-19. Based on the analysis of four public data sets of single-cell RNA-Seq on COVID-19 patients, we concluded that JUN, LST1 genes may play a role in the effect of ARB on COVID-19-related mortality, whereas CALM1 gene may contribute to the effect of CCB on COVID-19-related mortality. Our results provide guidance on the selection of antihypertension drugs for hypertensive patients infected with COVID-19.