The aim of this study was to evaluate the efficacy and safety of flumatinib in later-line treatment of Chinese patients with Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia ((CP-CML) previously treated with tyrosine kinase inhibitors (TKI). Patients with CML-CP were evaluated for probabilities of responses, including complete hematologic response (CHR), cytogenetic response, and molecular response (MR), and adverse events after the later-line flumatinib therapy. Of 336 enrolled patients with a median age 50 years, the median duration of treatment with flumatinib was 11.04 months (range, 2-25.23). Patients who achieved clinical responses at baseline showed maintenance of CHR, complete cytogenetic response (CCyR) or 2-log molecular response (MR2), major molecular response (MMR), and 4-log molecular response or deep molecular response (MR4/DMR) in 100%, 98.9%, 98.6%, and 92.9% of patients, respectively. CHR, CCyR/MR2, MMR, and MR4/DMR were achieved in 86.4%, 52.7%, 49.6%, and 23.5% of patients, respectively, who lacked the respective clinical responses at baseline. The patients without response at baseline, treated with flumatinib as a second-line TKI, having no resistance to prior TKI or only resistance to imatinib, with response to last TKI, and with BCR::ABL ≤10% had higher CCyR/MR2, MMR, or MR4/DMR rates. The adverse events observed during the later-line flumatinib treatment were tolerable and consistent with those reported with the first-line therapy. Flumatinib was effective and safe in patients who were resistant or intolerant to other TKI. In particular, second-line flumatinib treatment induced high response rates and was more beneficial to patients without previous second-generation TKI resistance, thus serving as a probable treatment option for these patients.