Tumor-associated macrophages (TAMs) are commonly considered accomplices in tumorigenesis and tumor development. However, the precise mechanism by which tumor cells prompt TAMs to aid in evading immune surveillance remains to be further investigated. Here, it is elucidated that tumor-secreted galectin-1 (Gal1) conferred immunosuppressive properties to TAMs. Specifically, patient specimens and a public database is first used to analyze the clinical relevance of Gal1 in hepatocellular carcinoma (HCC). Then, it is demonstrated that TAMs functioned as a critical mediator in the Gal1-induced progression of HCC and the establishment of an immunosuppressive tumor microenvironment. Furthermore, RNA-sequencing determined that Gal1 promoted the upregulation of chemokine (C-C motif) ligand 20 (CCL20) in TAMs via activating the PI3K/AKT/NF-κB pathway. Employing an anti-CCL20 neutralizing antibody and Foxp3DTR mice, it is demonstrated that CCR6