Based on reports from the International Agency for Research on Cancer (IARC) in 2008, it has been found more than 12 million new cancer cases in the world. We need an effort to discover new anticancer drugs from natural substance origin. Chlorogenic acid was isolated from Lampung Robusta coffee(Coffea Robusta). Pure experimental design in vitro using a Cell Lines Hep-G2 was conducted in the Department of Molecular Biology Cancer Hospital Dharmais. The aim of this study was to know the action mechanism of chlorogenic acid. In vitro study was using Hep-G2 cells and samples were divided into four groups; 2 control group treatment, 1 experiment group exposed to 727μM chlorogenic acid, 1 experiment group exposed to doxorubicin 1.5μM, and group treatment have been treated with 3times repetition. The expression of caspase 3 was examined at 0,8, 18 and 24. Data were analyzed with livaks method and repeated measurement. This study shows an increasing expression of caspase 3 from 0-8 hours. Caspase 3 shows the highest expression at 8 hours after doxorubicin exposure, with expression value 4.36 followed by chlorogenc acid it expression value 0.74. The caspase 3 expression was decreased after 8 hours up to 24 hours after either doxorubicin or chlorogenic acid exposure. Conclusion, IC50 doxorubicin (1.5μM) is moretoxic than chlorogenic acid (727μM). At 8 hours after doxorubicin and chlorogenic acid exposure, caspase 3 expression with doxorubicin (4,36) higher than chlorogenic acid (0.74).