Previous studies have shown that orlistat can effectively inhibit the proliferation, invasion, and migration of colon cancer cells.[43, 44] In our study, orlistat interfered with the interaction between HACD2 and PRKN by binding to HACD2 (KD = 0.13 μm), which further inhibited the expression of PKM2 and c‐Myc and reduced the proliferation of PC cells, especially in combination with gemcitabine (GEM) (Figure 7). The gene discussed is HACD2; the disease is malignant colon neoplasm.