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Tyrosine Kinase Inhibitor is still the main therapy in Chronic Myeloid Leukemia (CML) but some cases showed a high degree of resistance to TKI due to autophagy mechanism in resistant stem cells. Chloroquine is a drug that has an anti-autophagy function. The aim of this study was to analyze the synergism of combination therapy of chloroquine and nilotinib in causing cell death in nilotinib-resistant CML and to compare the differences in the percentage of cell death in nilotinib-resistant CML between single nilotinib therapy and combination of nilotinib and chloroquine. The methode used in this study was in-vitro laboratory experimental test using peripheral mononuclear blood cells isolated from 4 nilotinib-resistant CML patients. The data was analyzed using CompuSyn software that identifiesd a combination index and one way ANOVA parametric test followed by post hoc test using tukey test. The result of the study based on combination index showed that combination of nilotinib and chloroquine had a synergistic effect in increasing nilotinib-resistant CML cell death whereas ANOVA showed significant differences between single-drug nilotinib vs combination of nilotinib and chloroquine (p<0,05). Based on the result of study, it can be concluded that the combination of nilotinib and chloroquine is synergistic in causing death to nilotinib-resistant CML cells and also increasing CML cell death compared to a single-drug of nilotinib.