The invention discloses a swelling-type hollow silk 
fibroin micro-needle 
drug delivery system and a preparation method thereof. According to the technical scheme of the preparation method, a swelling modified silk 
fibroin solution is casted in a PDMS mold to be vacuumized, dried and molded as a hollow needle-type housing. After that, a silk 
fibroin micro-needle array provided with cavities in the hollow needle-type housing is filled with 
powder-like or solution-like drugs, vacuumizing and 
drying are carried out to form a 
drug part. Finally, a layer of modified silk fibroin solution is cast, dried and molded as a cladded 
coating. The cladded 
coating is removed to obtain the swelling-type hollow silk fibroin micro-needle 
drug delivery system. The drugs are wrapped inside the cavities of the silk fibroin micro-needle arrays, so that the 
system is high in drug 
loading ratio and low in 
skin allergenicity and stimulation. The 
system facilitates the sustained release and the 
controlled release of micro-needle drugs. Meanwhile, according to the preparation method, since the swelling modified silk fibroin solution is cast, dried and molded in a mild 
processing condition, the 
system is low in 
processing cost and suitable for large-scale production. Drugs are directly wrapped in the cavities of the swelling hollow micro-needles, so that controlled-release drugs are swelled in the micro-needle base material. In this way, the biological activities of the controlled-release drugs are maintained, while the structure of the hollow silk fibroin micro-needle 
drug delivery system is greatly simplified. The system is better in practicality.