Colorectal cancer (CRC) is a lethal malignant tumor and 25–30% of CRC patients develop liver metastasis (LM) with a worse prognosis, but the metastasis mechanism is yet elucidated. To identify the potential immune regulatory mechanism of CRC liver metastasis, single-cell sequencing and multiplex immunohistochemistry were applied to identify key cell populations of the tumor microenvironment (TME) in the CRC and LM sites. We found memory CD8+ T cells, B cells, and CTSB + macrophages were enriched in the LM site, forming the memory immune hub, which was important for the anti-tumor response against LM. Therefore, our results revealed that memory immune responses were called in the LM sites and probably meditated by CTSB + macrophages. • Multi-omics methods including scRNA-seq, mIHC and transcriptomics were performed to profile the CRC and the corresponding liver metastasis sites. • Memory CD8+ T cell and memory B cell response recalled in the liver metastasis sites. • CTSB + macrophages repress anti-tumor immune response through several immune checkpoints. [ABSTRACT FROM AUTHOR]