In this study, in order to explore the detailed relationships and related mechanisms, we used tissue microarray (TMA), spatial transcriptomic sequencing and single-cell sequencing to assess the complex TME mediated by CCL21/CCR7 axis with 2 cohorts (n1 = 240, n2 = 382, Zhongshan Hospital), 6 tumors and paired adjacent liver tissues from HCC patients, as well as pre-clinical experiments in vivo and in vitro, using CRISPR-cas9 system to establish CCR7 knock-out (KO) HCCLM3 cell line. Here, CCL21 is linked to hepatocellular carcinoma.