〔Abstract〕 Objective To investigate the effect of antimicrobial peptide LL-37 on apoptosis of colon carcinoma HT-29 cells and its molecular mechanism. Methods Colon cancer HT-29 cells were treated with antimicrobial peptide LL-37 at different concentrations of 50 μg/ml,100 μg/ml and 200 μg/ml or LL-37 combined with AMPK inhibitor dorsomorphin(10 μmol/L, pre-treated for 30 min) for 48 h. The apoptosis rate of HT-29 cells was assessed by flow cytometry. Apoptotic proteins(Bcl-2 and Bax), autophagy-related proteins(Beclin1, Atg5, LC3 I and LC3 II) and AMPK protein were detected by Western blot assay. Results High dose antimicrobial peptide LL-37 could promote apoptosis of HT-29 cells in colon carcinoma(P<0.05), and increase the expression of autophagy related proteins Beclin1, Atg5 and LC3 II/LC3 I(P<0.05), accompanied by abnormal activation of AMPK(P<0.01). Intervention of AMPK inhibitor dorsomorphin combined with LL-37 could reverse the effect of antimicrobial peptide LL-37 on HT-29 cells in colon carcinoma. Conclusion Antimicrobial peptide LL-37 promotes apoptosis of colon cancer cell line HT-29 by activating AMPK-mediated autophagy.