The present invention discloses a crystal form, a preparation method and an application of a 4' -substituted nucleoside compound I having the following structure, including salts, prodrugs, and compositions thereof. Animal pharmacokinetic studies demonstrated that the effective drug concentrations of Compound Ia and Compound Ig in HIV target cells, peripheral blood mononuclear cells (PBMC), were effective in inhibiting HIV replication after 7 and 5 days, respectively. Therefore, Compound I can be used as a long-acting drug for preventing and treating AIDS. R is selected from ethynyl, azide, and cyano groups, X is selected from hydrogen and fluorine, and B is selected from B1 and B2.