Abstract: HPLC-RID and HPIC-CD methods were established for the determination of sucrose octasulfate content in irinotecan hydrochloride liposomes for injection. HPLC-RID:This method was performed on a Kromasil 100-5-NH₂ column (250 mm×4.6 mm, 5 μm) with a mobile phase of 0.8 mol·L^-1 ammonium sulfate buffer (pH 3.5)-acetonitrile (83:17). The flow rate, column temperature and detector temperature were maintained at 1 mL·min^-1, 30℃ and 30℃ respectively. HPIC-CD:This method was performed on an anion exchange column Dionex InPac^TM AS11-HC (250 mm×4 mm, 9 μm) with an eluent of 30 mmol·L^-1 sodium hydroxide solution. The flow rate was 1.5 mL·min^-1, the column temperature was 30℃ and the detector temperature was 35℃. The HPLC-RID method and HPIC-CD method were validated with respects to specificity, limit of detection, limit of quantitation, linearity, precision, accuracy, stability and robustness and met the validation requirements. There were no significant differences between the HPIC-CD and HPLC-RID methods according to T-test analysis, both of which were applicable for the measurement of sucrose octasulfate concentration in irinotecan hydrochloride liposomes for injection. However, the HPLC-CD was better at the following aspects:higher detection sensitivity, simpler sample pretreatment, lower time and money spent, better environmental protection.