Background: Leishmaniasis is a globally widespread parasitic infection, and the resistance of the parasite causing this infection to commonly used drugs has become a serious problem. Therefore, it has become necessary to conduct studies on the role of alternative medicines as a treatment for this disease. Objective: This study aimed to determine the effect of using Capparis spinosa extract on the gene expression of HSP70 and LACK genes in promastigote. Method: The parasite was cultured in RPMI-1640 culture medium in the laboratory under suitable working condition. Subsequently, the parasite was exposed to different concentration of Capparis spinosa extract, and then the gene expression of the parasites HSP70 and LACK was measured by used RT-PCR assay. Results: Exposure of promastigote to different concentrations of Capparis spinosa extract resulted in a significant increase in the Gene expression of HSP70 and LACK genes compared to the control group suggesting the potential use of this extract as a treatment for leishmaniasis. Conclusion: The current study showed that Capparis spinosa extract has an effect on HSP70 and LACK genes expression through the effect of some chemical compounds of the plant extract on protein synthesis and iron chelation.