Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease, with liver metastasis being the primary cause of death. Efferocytosis, the engulfment of apoptotic cells by macrophages, is a critical process in tissue homeostasis and wound healing but its role in metastasis is less understood. This study found that the colonization of the hepatic metastatic site is accompanied by low-grade tissue injury, and efferocytosis-mediated clearance of parenchymal dead cells promotes macrophage reprogramming and liver metastasis. Mechanistically, progranulin expression in macrophages is necessary for efficient efferocytosis by controlling lysosomal acidification via cystic fibrosis transmembrane conductance regulator and the degradation of lysosomal cargo, resulting in LXRα/RXRα-mediated macrophage conversion and upregulation of arginase1. Pharmacological blockade of efferocytosis or macrophage-specific genetic depletion of progranulin impairs macrophage conversion, improves CD8+ T cell functions, and reduces liver metastasis. These findings reveal how hard-wired functions of macrophages in tissue repair contribute to liver metastasis and identify potential targets for preventing PDAC liver metastasis.Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease, with liver metastasis being the primary cause of death. Efferocytosis, the engulfment of apoptotic cells by macrophages, is a critical process in tissue homeostasis and wound healing but its role in metastasis is less understood. This study found that the colonization of the hepatic metastatic site is accompanied by low-grade tissue injury, and efferocytosis-mediated clearance of parenchymal dead cells promotes macrophage reprogramming and liver metastasis. Mechanistically, progranulin expression in macrophages is necessary for efficient efferocytosis by controlling lysosomal acidification via cystic fibrosis transmembrane conductance regulator and the degradation of lysosomal cargo, resulting in LXRα/RXRα-mediated macrophage conversion and upregulation of arginase1. Pharmacological blockade of efferocytosis or macrophage-specific genetic depletion of progranulin impairs macrophage conversion, improves CD8+ T cell functions, and reduces liver metastasis. These findings reveal how hard-wired functions of macrophages in tissue repair contribute to liver metastasis and identify potential targets for preventing PDAC liver metastasis.