The findings indicated that miR-183-5p delivered by EVs from HCC cells is crucial in mediating the communication between HUVECs and HCC cells by modulating the SIK1/PI3K/AKT and CCL20/CCR6 signaling pathways, and EVs-miR-183-5p might be a potential therapeutic target for HCC patients. Here, SIK1 is linked to hepatocellular carcinoma.