Objective To investigate the predictive value of lipid levels on response to therapy in patients with chronic myeloid leukemia in chronic phase (CML-CP). Methods The clinical data of 453 patients with CML-CP were retrospectively analyzed. The median age was 46 (5-90) years and 64.2% male. Serum lipid levels were compared between groups. Logistic regression models were applied to analyze prognostic-related factors. Results Patients with CML showed low total cholesterol (TC), high-density cholesterol lipoprotein (HDL-C), and low-density cholesterol lipoprotein (LDL-C) levels and high triglyceride (TG), TC/HDL-C, non-HDL-C/HDL, and TG/HDL-C levels compared with normal controls (p<0.0001), and no significant difference in LDL-C/HDL-C (p>0.05). The changes of blood lipid profiles in different age groups were consistent with the overall trend, and post-menopausal patients showed high levels of TG and LDL-C . Lipid levels recovered significantly at the time of achieving major molecular response (MMR) and deep molecular response (DMR) compared to the initial diagnosis. Patients with DMR showed lower LDL-C, TC/HDL-C, LDL-C/HDL-C, and non-HDL-C/HDL compared to patients with MMR (p<0.05). Multivariate logistic regression analysis showed that LDL-C/HDL-C (OR=0.511, 95%CI: 0.330-0.793, p=0.003), Sokal risk score (p=0.016) and duration of TKI treatment (OR=1.025, 95% CI: 1.013-1.037, p<0.0001) were significantly associated with the achievement of DMR. Conclusions Lipid metabolism is disturbed in patients with newly diagnosed CML and TKI is effective in reversing the lipid profile. Lipid level monitoring is important for efficacy assessment in CML patients and LDL-C/HDL-C can be used as an independent predictor of DMR.