When coronavirus disease 2019 (COVID-19) became a pandemic, one of most important questions was whether people who smoke are at more risk of COVID-19 infection. A number of clinical data have been reported in the literature so far, but controversy exists in the collection and interpretation of the data. Particularly, there is a controversial hypothesis that nicotine might be able to prevent SARS-CoV-2 infection. In the present study, motivated by the reported controversial clinical data and the controversial hypothesis, we carried out cytotoxicity assays in Vero E6 cells to examine the potential cytoprotective activity of nicotine against SARS-CoV-2 infection and demonstrated for the first time that nicotine had no significant cytoprotective activity against SARS-CoV-2 infection in these cells.