Objective To discuss the effects of geniposide on proliferation, apoptosis, and autophagy in lung cancer cells by regulating the adenosine monophosphate-activated protein kinase (AMPK) / mammalian target of rapamycin (mTOR) / unc-51 like kinase 1 (ULK1) pathway. Methods A549 cells were divided into lung cancer,low-dose geniposide, medium-dose geniposide, high-dose geniposide, AMPK activator (MK8722), and high-dose geniposide+AMPK inhibitor (Compound C) groups. 5-Ethynyl-2’ deoxyuridine (EdU) staining and CCK-8 assays were used to detect cell proliferation. Flow cytometry was used to detect cell apoptosis. Transmission electron microscopy was used to count autophagosomes in A549 cells. RT-qPCR was used to detect the mRNA expression of proliferating cell nuclear antigen ( PCNA), p53, p62, and Bcl-2 homologous domain protein ( Beclin1) in A549 cells. Western blot was used to detect microtubule associated protein 1 light chain 3 (LC3), p-AMPK, p-mTOR, and p-ULK1 in A549 cells. Results Compared with levels in the lung cancer group, the low-, medium-, and high-dose geniposide groups showed decreases in the EdU-positive rate, OD₄₅₀ value, PCNA and p62 mRNA levels, and pmTOR protein expression in A549 cells and increases in the apoptosis rate, autophagosome number, p53 and Beclin1 mRNA levels, and LC3-II/ LC3-I, p-AMPK, and p-ULK1 protein levels; the high-dose geniposide group showed the most prominent differences (P<0. 05). Compared with levels in the lung cancer group, the MK8722 group showed decreases in the EdU-positive rate, OD₄₅₀ value, PCNA and p62 mRNA levels, and p-mTOR protein expression in A549 cells and increases in the apoptosis rate, autophagosome number, p53 and Beclin1 mRNA levels(P<0. 05), and LC3-II/ LC3-I, p-AMPK, and p-ULK1 protein levels ( P< 0. 05). Compared with levels in the high-dose geniposide group, the high-dose geniposide+Compound C group showed increases in the EdU-positive rate, OD₄₅₀ value, PCNA and p62 mRNA levels, and p-mTOR protein levels in A549 cells and decreases in the apoptosis rate,autophagosome number, p53 and Beclin1 mRNA levels ( P< 0. 05), and LC3-II/ LC3-I, p-AMPK, and p-ULK1 protein levels (P<0. 05). Conclusions Geniposide may inhibit A549 cell proliferation and promote autophagy and apoptosis through activating the AMPK/ mTOR/ ULK1 pathway.