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Current breast cancer treatment has shifted to using natural ingredients such as C. zedoaria high potential and low side effect. Previous studies have identified that compounds in C. zedoaria are capable as anti-proliferative, increasing apoptosis and anti-metastasis. However, information the mechanism of roles its active compound for CXCR4 inhibition in the carcinogenesis process unknown. C_X_C chemokine receptor type 4 (CXCR4) is an alpha-chemokine receptor specific for stromal-derived-factor-1 (SDF-1/CXCL12). CXCR4 has been reported to play an important role for prognosis and potential drug target in breast cancer. This study aimed to analyze the potential effect of active compound from C. zedoaria as breast cancer chemotherapeutic agents through CXCR4 inhibition. Binding affinity analysis through molecular docking shows that 11 active compounds have the potential inhibiting CXCR4 with smallest binding affinity and same binding site with Chalcone and Epirubicin. However, Stigmasterol, Campesterol, and β-sitosterol have lowest binding affinity than the other active compound. Protein interaction analysis illustrates that CXCR4 can interact with various protein, including CXCL12, STAT3, and JAk2, used as a diagnostic marker and poor prognosis factor for cancer. These data indicate that active compounds from C. zedoaria highly potential as anti-breast cancer. Additional research is needed to validate above data.