Objective To investigate the inhibitory effect of micro RNA-34a-5p(miR-34a-5p)on oxidative stress damage of macrophages by targeting murine double minute 4(MDM4).Methods THP-1 human mononuclear cells were cultured and differentiated into macrophages after resuscitation.A blank control group was set up.The remaining cells were added to human oxidized low-density lipoprotein,incubated for 48 h,and differentiated into macrophage foam cells.AS control group was set up.miR-34a-5p plasmid transfection group was set as miR-34a-5p plasmid transfection.There were 24 replicates per group.The apoptosis of macrophages,the levels of MDA,SOD protein and ROS,and the positive rate of MDM4 were compared among the three groups.Results The apoptosis rate was(2.55±0.32)%in the blank control group,(28.16±4.23)%in the AS control group,and(13.48±1.66)%in the miR-34a-5p transfection group,the difference among the three groups was statistically significant(P<0.05).AS control group was higher than blank control group and miR-34a-5p trans-fection group,and miR-34a-5p transfection group was higher than blank control group,with statistical significances(P<0.05).There were statistically significant differences in MDA,SOD protein and ROS levels among the three groups(P<0.05).MDA and ROS levels were the highest and SOD levels were the lowest in AS control group,followed by miR-34a-5p transfection group,with statistical significances(P<0.05).MDM4 positivity rate was(8.33±0.35)%in the blank control group,(29.26±3.48)%in the AS control group,and(14.26±1.59)%in the miR-34a-5p transfection group,the difference among the three groups was statistically significant(P<0.05).Conclusion MiR-34a-5p can down-regulate MDM4 and in-hibit the oxidative stress damage of macrophages.