Abstract: As the first-line therapy of malignant tumor, gemcitabine is compromised by inability to be taken orally, rapid metabolism by deaminase, low bioavailability and easy development of drug resistance. To circumvent these shortcomings, researchers have devoted continuous efforts to structure modification of gemcitabine using prodrug strategy. This review summarizes the latest advances in gemcitabine derivatives and expects to provide reference for the development of new gemcitabine derivatives to overcome clinical shortcomings.