The melting temperature, melting enthalpy, and specific heat capacities (Cp) of 5′-deoxy-5′-iodo-2′,3′-O-isopropylidene-5-fluorouridine (DIOIPF) were measured using DSC-60 Differential Scanning Calorimetry. The melting temperature and melting enthalpy were obtained to be 453.80 K and 33.22 J g−1, respectively. The relationship between the specific heat capacity and temperature was obtained to be Cp/J g−1 K−1 = 2.0261 – 0.0096T + 2 × 10−5 T2 at the temperature range from 320.15 to 430.15 K. The thermal decomposition process was studied by the TG–DTA analyzer. The results showed that the thermal decomposition temperature of DIOIPF was above 487.84 K, and the decomposition process can be divided into three stages: the first stage is the decomposition of impurities, the mass loss in the second stage may be the sublimation of iodine and thermal decomposition process of the side-group C4H2O2N2F, and the third stage may be the thermal decomposition process of both the groups –CH3 and –CH2OCH2–. The obtained thermodynamic basic data are helpful for exploiting new synthetic method, engineering design, and commercial process of DIOIPF.