Title: Kill two birds with one stone: Reprogramming tumor microenvironment with growth differentiation factor 11. In this letter the authors highlighted and discussed study by Escobedo-Calvario et al (WJG 2025;31:111307), which demonstrated that the protein growth differentiation factor 11 (GDF-11) effectively “re-educates” pro-tumoral macrophages by reducing classic M2 markers, changing cellular metabolism, and boosting production of reactive oxygen species, which ultimately switch the macrophages from a pro-tumor toward an anti-tumor state. Importantly, when applied to HCC cells, GDF-111also reduced the cancer cells’ capacity to proliferate and migrate – essential for metastasis.