Luteolin (3,4,5,7‑tetrahydroxyflavone) is a natural flavonoid that has been found to exhibit anticancer properties in certain types of cancers. In the present study, the role of luteolin and its underlying mechanisms were explored in colorectal cancer (CRC) cells. First, the effects of luteolin on CRC cells proliferation, migration and invasion were examined by CCK‑8, wound healing and Transwell assays, respectively. It was demonstrated that luteolin had no effects on CRC cells proliferation while inhibited cells migration and invasion both in vitro and in vivo. Then, expression of pleiotrophin (PTN) and miR‑384 was detected in cells and CRC tissues by qPCR. Luteolin was found to upregulate miR‑384 and downregulate PTN expressions both in CRC cells and tissues. miR‑384 inhibition and PTN overexpression partially reversed the inhibition of HT‑29 cells migration and invasion induced by luteolin. Target analysis revealed that miR‑384 directly regulates PTN expression. The correlation analysis between PTN expression and clinical characteristics revealed that PTN expression was positively related to cancer progression. The present study demonstrated that luteolin exerts anticancer effects against CRC cells by modulating PTN via miR‑384 expression suggested that PTN may serve as a promising candidate for therapeutic applications in CRC treatment.