Expression of lectin galactoside‐binding soluble 3 (LGALS3), a member of the galectin family of carbohydrate‐binding proteins, is frequently upregulated in various solid and blood malignancies and plays broad roles in cancer progression through distinct intracellular and extracellular mechanisms.[12] Recently, cancer‐secreted LGALS3 has emerged as an important regulator in modulation of tumor microenvironment and correlated with metastasis.[13] In this study, we found that HCC‐secreted LGALS3 induced HCC bone‐metastasis and SREs by facilitating the formation of a pre‐metastatic niche. This evidence concerns the gene LGALS3 and hepatocellular carcinoma.