Objective To investigate the effect of miR-22-3p on pyroptosis of vascular smooth muscle cells (VSMCs) induced by homocysteine (Hcy). Methods Human VSMCs were cultured in vitro and divided into a Control group (0 μmol/L Hcy) and a Hcy group (100 μmol/L Hcy). After intervention, expression levels of pro Caspase-1,gasdermin D (GSDMD), N-GSDMD, and NLR family pyrin domain containing 3 (NLRP3) were detected by Western blot. MiR-22-3p expression was determined by quantitative real-time reverse-transcription polymerase chain reaction. Interleukin (IL)-1β and IL-18 levels in the supernatant were measured by enzyme-linked immunosorbent assay. Cells were also transfected with control miR-22-3p (miR-22-3p-NC), miR-22-3p-mimic, and miR-22-3p-inhibitor, to observe the effects on VSMC pyroptosis induced by Hcy. Results Expression levels of pro Caspase-1, GSDMD, N-GSDMD, and NLRP3 in VSMCs were increased (P<0.05), IL-1β and IL-18 levels were increased (P<0.01), and the relative expression level of miR-22-3p was reduced (P<0.01) in the Hcy group compared with the Control group. Transfection with miR-22-3p-mimic significantly decreased the expression levels of pro Caspase-1, GSDMD, N-GSDMD, and NLRP3 in VSMCs (P<0.01), and significantly decreased levels of IL-1β and IL-18 (P<0.01), while transfection with miR-22-3p inhibitor significantly increased the expression levels of pro Caspase-1, GSDMD, N-GSDMD, and NLRP3 in VSMCs (P<0.01) and significantly increased the levels of IL-1β and IL-18 (P<0.05). Conclusions MiR-22-3p may delay Hcy induced VSMC pyroptosis.