Background COVID-19 is a highly infectious respiratory disease. No effective therapeutics have yet been proved for treating of severe COVID-19. Objectives To determine whether human Umbilical Cord Mesenchymal Stem Cells infusion may be effectiveness and safety in the treatment of severe COVID-19. Methods The severe COVID-19 randomly divided into 2 groups, standard treatment group and standard treatment plus hUC-MSCs infusion group. The incidence of severe patients aggravated to critically illness, 28-day mortality, clinical symptoms improvement, time to clinical symptoms improvement, hematologic indicators including C-reaction protein, lymphocyte number, interleukin 6 and imaging changes were observed and compared between two groups. Measurements and Main Results The incidence of severe patients aggravated to critically illness and 28-day mortality were 0 in hUC-MSCs treatment group, while 4 patients in control group were deteriorated to critical illness and been used invasive ventilation, 3 of them died, and 28-day mortality was 10.34%. In hUC-MSCs treatment group, the time to clinical improvement was shorter, clinical symptoms of weakness and fatigue, shortness of breath, and low oxygen saturation had improved obviously began the third day of stem cells infusion, and reached the significant difference on the day 7, CRP and IL-6 were significantly decreased from day 3 of infusion, the time for lymphocyte count returned to normal range was significant faster, and lung inflammation absorption was significantly shorter from CT imaging. Conclusions Intravenous transplantation of hUC-MSCs is a safe and effective way that can be considered as salvage and priority choice in the treatment of severe COVID-19.