Cancer metastasis accounts for the majority of cancer-related deaths and remains a clinical challenge. Metastatic cancer cells generally resemble cells of the primary cancer, but they may be influenced by the milieu of the organs they colonize. Here, we show that colorectal cancer cells undergo metabolic reprogramming after they metastasize and colonize the liver, a key metabolic organ. In particular, via GATA6, metastatic cells in the liver upregulate the enzyme aldolase B (ALDOB), which enhances fructose metabolism and provides fuel for major pathways of central carbon metabolism during tumor cell proliferation. Targeting ALDOB or reducing dietary fructose significantly reduces liver metastatic growth but has little effect on the primary tumor. Our findings suggest that metastatic cells can take advantage of reprogrammed metabolism in their new microenvironment, especially in a metabolically active organ such as the liver. Manipulation of involved pathways may affect the course of metastatic growth. Display omitted •Colon cancer liver metastasis upregulates ALDOB, an enzyme for fructose metabolism•Metabolized fructose provides fuel for the central carbon metabolism•Targeting ALDOB or its upstream regulator GATA6 reduces liver metastasis growth•Reducing dietary fructose diminishes liver metastatic growth Bu et al. show that, during colonization of the liver, the liver environment can cause colon cancer cells (CRC) to undergo metabolic reprogramming by upregulating aldolase B, which enhances fructose metabolism and promotes growth of CRC liver metastases. Targeting aldolase B or reducing dietary fructose reduces liver metastasis growth.