As a neuraminidase inhibitor, oseltamivir has effectively combated the pandemic influenza A and B, so it is a first-line commonly used antiviral drug, especially in primary hospitals. At the same time, oseltamivir, as an over-the-counter drug, is also a popular antiviral drug. As healthcare workers fighting against coronavirus disease 2019 (COVID-19), we have found that many patients experiencing discomfort or considered to be infected with a virus take oseltamivir. From severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 to middle east respiratory syndrome coronavirus (MERS-CoV) in 2012, and now the current COVID-19 epidemic, there is not plenty of evidence showing that oseltamivir is effective against coronavirus. Still, there is also no sufficient evidence to refute its ineffectiveness. We cannot predict whether there will be a pandemic of respiratory coronavirus in the future, so we hope to initiate such research and preliminarily explore whether oseltamivir is effective for COVID-19, which can better guide healthcare workers in the selection of appropriate antiviral drugs in the face of coronavirus epidemics. If oseltamivir is effective, then a wide promotion of its application often can achieve a double effect with half the effort. If it is not effective, then considering the side effects of oseltamivir, it is not necessary to use unreasonable drugs that will not slow the progression of the disease but can cause adverse reactions. We found that oseltamivir is not suitable for fighting against COVID-19 through the method of computer aided drug design and in vitro study and retrospective case study. Meanwhile it was high-occurrence seasons for the influenza, COVID-19 should be highly suspected in patients who did not benefit from oseltamivir. We hope that the result of our study could be shared with the frontline physicians in fighting against COVID-19.