The triggering receptors expressed on myeloid cells (TREMs) family of cell surface receptors are mainly expressed by myeloid cells. The expression profile of TREM-like 2 (TREML2), a TREM family member, in patients with acute myeloid leukemia (AML) is unknown. In this study, we aimed to elucidate the role of TREML2 in the development of AML. We analyzed the TREML2 expression profile in patients with AML. TREML2 was expressed at lower levels in patients with AML than in healthy individuals. The partial remission (PR) + no remission (NR) group showed lower TREML2 expression levels and a poorer chemotherapy response than that observed in the complete remission group. Overall survival was significantly shorter in the group with low TREML2 expression levels than in the group with high TREML2 expression levels. TREML2 inhibited the proliferation of AML cells and enhanced the sensitivity of AML cells to doxorubicin. Mechanistically, TREML2 reduced C-X-C motif chemokine ligand 10 expression levels by inhibiting the nuclear factor kappa B pathway. Taken together, we demonstrate that TREML2 has diagnostic value as a potential indicator of AML and that upregulation of TREML2 may be a new strategy to overcome doxorubicin resistance for AML treatment.