ABSTRACT Aim and Scope: Prostate cancer will occur when immortal cells develop in the prostate gland. It was frequently diagnosed in men and becomes the fourth most common cancer in the world in 2014. In Indonesia, it has high prevalence of about 16 cases in 100,000 of men. Furthermore, Indonesia has an endemic plant called Pasak Bumi (Eurycoma longifolia Jack) which is well-known as traditional medicine and cancer therapy. The root extract of Pasak Bumi consists of eurycomanone, quassinoid, and canthin. Therefore, this study aimed to predict the potency of E. longifolia active compounds as prostate cancer therapy. Material and Methods: There are four essential protein targets in prostate cancer such as Bcl-2, RAS, MAPK, and CASP. The three-dimensional structure of active compounds was retrieved from PubChem, and protein target was downloaded from Protein Data Bank. The interactions were calculated using Pyrx.0.8. Thus, the molecular interaction was analyzed using LigPlus. Moreover, the biological activity of the active compound was analyzed using PASS server. Results and Discussion: Results showed that each active compound is strongly bind to RAS and only RAS -quassinoid complex which has the lowest binding affinity score about −9.3 Kcal/mol. Based on the structure-activity relationship analysis, only eurycomanone and quassinoid which potentially involved in the anticancer mechanism as antineoplastic and apoptosis agonist. It means these compounds are blocking the active site of RAS protein to inhibit the cell proliferation. Conclusion: It can be concluded that all active compounds have the lowest binding affinity to RAS. Moreover, quassinoid is the most active compounds which have the influence to RAS. It shows that quassinoid potentially as a therapeutic agent. KEY WORDS: Anticancer, Apoptosis, Canthin, Eurycomanone, Herbal compound, Inhibitor, Prostate cancer, Quassinoid