One embodiment of the present invention provides an operation method of a memory device. The memory device includes a source, a drain, and a channel region between the source and the drain, a gate dielectric with a charge storage layer on the channel region, and a gate on the gate dielectric, wherein the source, the drain and the channel region are located in a substrate. The operation method includes the following steps: applying a reverse bias between the gate and the drain of the memory device to generate band-to-band hot holes in the substrate near the drain; injecting the band-to-band hot holes to a drain side of the charge storage layer; and performing a program/erase operation upon the memory device. The band-to-band hot holes in the drain side of the charge storage layer are not completely vanished by the program/erase operation.