The invention discloses a benzenesulfonyl furazan modified gemcitabine derivative and a preparation method and use thereof. The benzenesulfonyl furazan modified gemcitabine derivative comprises a compound as shown in a universal formula I and pharmaceutically acceptable salts thereof. According to the rational drug design principle and the combination principle, the clinical pharmacology activity of gemcitabine is retained; meanwhile, with gemcitabine as a lead compound, a benzenesulfonyl furazan NO donor is respectively coupled to N4 amino of gemcitabine through different linking groups to synthesize a benzenesulfonyl furazan modified NO donor type gemcitabine derivative, in order to obtain a compound with stronger anti-tumor activity and better bioavailability than gemcitabine.