Acute lung injury (ALI) represents the most severe form of the viral infection sustained by coronavirus disease 2019 (COVID-19). Today, it is a pandemic infection, and even if several compounds are used as curative or supportive treatment, there is not a definitive treatment. In particular, antiviral treatment used for the treatment of several viral infections (eg, hepatitis C, HIV, Ebola, severe acute respiratory syndrome-coronavirus) are today used with a mild or moderate effect on the lung injury. In fact, ALI seems to be related to the inflammatory burst and release of proinflammatory mediators that induce intra-alveolar fibrin accumulation that reduces the gas exchange. Therefore, an add-on therapy with drugs able to reduce inflammation, edema, and cell activation has been proposed as well as a treatment with interferon, corticosteroids or monoclonal antibodies (eg, tocilizumab). In this article reviewing literature data related to the use of escin, an agent having potent anti-inflammatory and anti-viral effects in lung injury, we suggest that it could represent a therapeutic opportunity as add-on therapy in ALI related to COVID-19 infection.