Taken together, these results indicated that MACC1 contributes to COAD progression and immune cell infiltration via the ZFAS1/miR-642a-5p/MACC1 axis, suggesting that the ZFAS1/miR-642a-5p/MACC1 axis may provide a novel therapeutic target and a valuable prognostic indicator for COAD. Here, MACC1 is linked to colon adenocarcinoma.