Cerasomes, a novel type of organic–inorganic liposomal nanohybrid with a silicate surface, has attracted a great deal of attention as a perfect substitute for liposomes due to its good morphological stability. In this paper, the capability of cerasomes as possible carriers for 10-hydroxycamptothecin (HCPT) delivery was investigated. Both cerasomes and composite cerasomes containing liposome-forming lipids (LFLs) were fabricated to evaluate their potential for the release of HCPT. It was found that composite cerasomes exhibited good encapsulation efficiency and a high loading content of HCPT compared with cerasomes. They also displayed a remarkable ability to maintain their size and optimize the release rate of HCPT, resulting in an improved drug pharmacokinetic profile in vivo. In vivo toxicity experiments showed that Wistar rats administered with cerasomes at a high dose of 50 mg kg⁻¹ displayed slight acute toxicity at 24 h; afterwards, the rats recovered from the side effects. No visualized tissue injury was found during the experimental period. All the results indicated that liposomal nanohybrid cerasomes may be a type of promising drug delivery platform for the sustained release of the anticancer drug HCPT in vivo.