Aim To investigate whether microRNA-20a-5p (miR-20a-5p) alleviates oxidized low density lipoprotein (ox-LDL)-induced injury of human umbilical vein endothelial cells (HUVEC) by targeting myocardin-related transcription factor A (MRTFA). Methods RT-qPCR was used to detect the expression of miR-20a-5p in HUVEC induced by ox-LDL of various doses at different time. MTT, flow cytometry and Western blot assays were performed to evaluate the effect of overexpression of miR-20a-5p and MRTFA on the ox-LDL-induced proliferation and apoptosis of HUVEC.Lactate dehydrogenase (LDH) kit was conducted to determine the effect of overexpression of miR-20a-5p on ox-LDL-induced LDH release in HUVEC. ELISA assay was employed to examine the effects of upregulation of miR-20a-5p and MRFA on ox-LDL-mediated changes of oxidative stress indexes superoxide dismutase (SOD), nitric oxide (NO), endothelial nitric oxide synthasee (eNOS) and malondialdehyde (MDA) in HUVEC. Luciferase reporter Western blot assays was introduced to validate the relationship between miR-20a-5p and MRTFA. Results The expression of miR-20a-5p was significantly decreased in a time or dose dependent manner. Overexpression of miR-20a-5p attenuated the effect of ox-LDL on proliferation, apoptosis, and LDH release in HUVEC. Upregulation of miR-20a-5p repaired ox-LDL-induced oxidative stress injury in HUVEC. MRTFA was a direct target gene of miR-20a-5p. MRTFA overexpression undermined the effects of miR-20a-5p on proliferation, apoptosis, and oxidative stress injury index in ox-LDL-treated HUVEC. Conclusion miR-20a-5p can repair ox-LDL-induced HUVEC damage via targeting MRTFA.