Objective: To investigate the proper concentration of isoliquiritigenin (ISL) on human cervical cancer (CC) cells (Siha) inhibition and find the possible mechanism. Materials and Methods: After been cultured for 24 hours, the Siha cells were grouped according to added: control group, ISL group (with the concentrations of 25, 50, 100, 200, 300, 400 ug/mL) and positive group (cisplatin 25 ug/mL), methyl thiazolyl tetrazolium (MTT) assay was performed to define the proper concentration of ISL for Siha cells inhibition. With the proper concentration of IST, the apoptosis and the changes of mitochondrial transmembrane potential were detected by flow cytometry. Meanwhile, the caspases (3/8/9) were detected by enzyme linked immunosorbent assay (ELISA). The effects of ISL on the gene expression of BCL-2, P53, P21, and E6 mRNA were detected by RT-PCR. Results: After been cultured with IST, the authors found that the inhibition rate increased the most with the concentrations of 50, 100, and 200 ug/mL; the apoptosis rates were 3.6% ± 0.76% (control), 26.1% ± 2.94% (ISL 50), 37.1% ± 1.44% (ISL 100), 60.0% ± 1.44% (ISL 200), and 74.2% ± 1.89% (positive), and the mitochonodrial transmembrane potential were 93.57% ± 0.76% (control), 80.53% ± 1.19% (ISL 50), 44.77% ± 2.06% (IST 100), 26.73% ± 1.56% (IST 200), 7.90% ± 0.26% (positive) of before, with a significant differences (p < 0.05); meantime the caspases' expression also increased with IST concentration increasing. Conclusions: The inhibition of IST on Siha cells is a time and concentration-dependent manner, the cell apoptosis increased with the concentration of ISL 50, 100, and 200 ug/mL which may be realized through inducing the mitochondrial membrane potential pathway, downregulating the expression of E6 and BCL-2, and upregulating the expression of p21 and p53 genes.