The purpose of this study is to investigate the influence of miR-128-3p on the formation of THP-1-derived foam cells. To this end, THP-1 cells were induced to differentiate into macrophages by phorbol 12-myristate 13-acetate (PMA) and divided into control group, oxidized low-density lipoprotein (ox-LDL) group, miR-NC group, miR-128-3p mimic group, and miR-128-3p mimic+nucleotide-binding oligomerization domain-containing protein 1 (NOD1) agonist (iE-DAP) group. Foam cell formation was induced by ox-LDL (100 μg/mL) after the corresponding transfection treatment. The expressions of miR-128-3p, NOD1 mRNA, and lipid accumulation in cells were examined and the content of cholesterol in cells and the levels of TNF-α and IL-6 in cell culture supernatants were detected. Protein expressions of NOD1, receptor-interacting protein 2 (RIP2), phosphorylated RIP2 (p-RIP2), NF-κB p65 (p65), and phosphorylated p65 (p-p65) in cells were measured. The targeting between miR-128-3p and NOD1 was validated. The results showed that compared to those of the control group, miR-128-3p level in the ox-LDL group was decreased (P<0.05), while the lipid content, cholesterol content, NOD1 mRNA and protein levels, p-RIP2/RIP2 and p-p65/p65 ratios, and the TNF-α and IL-6  levels in the cells were all increased (P<0.05). Compared to those of the ox-LDL group, the expression of miR-128-3p in the miR-128-3p mimic group was increased (P<0.05), while the expression of NOD1, the phosphorylation of RIP2 and p65, the accumulation of lipid and cholesterol, and the levels of TNF-α and IL-6 were all decreased (P＜0.05). Compared to those of the miR-128-3p mimic group, the expression of NOD1, the phosphorylation of RIP2 and p65, the accumulation of lipid and cholesterol, and the levels of TNF-α and IL-6  were all increased in the miR-128-3p mimic+iE-DAP group (P＜0.05). Compared to cells transfected with miR-NC, cells transfected with miR-128-3p mimic showed decreased activity of luciferase reporter gene containing NOD1-WT (P<0.05). This study suggests that overexpression of miR-128-3p may inhibit the formation of THP-1-derived foam cells by inhibiting the NOD1/RIP2 signaling pathway.