An irinotecan hydrochloride composite phospholipid composition, preparation method and uses thereof in the preparation of drugs for treating tumors or drug resistant tumors. The composite phospholipid composition comprises irinotecan hydrochloride, composite phospholipid, cholesterol, long-circulating membrane material, surfactant and a buffer medium. The composition improves stability of lipid formulation and the anti-tumor effect of irinotecan hydrochloride, and can overcome multidrug resistance of a tumor.