Granite has relatively low-permeability and it has been considered as one of favorable geological formation for final disposal of high-level radioactive waste (HLW). However, the granite is often fractured and characterized as complex discrete fracture-matrix systems with considerable degree of uncertainties in its physical and geometrical properties. Prediction of nuclide migration in fractured granite at large spatial and long temporal scales is important for safety assessment of HLW disposal. In the present study, parametric studies are performed to evaluate the long-term barrier performance of fractured granite using the Beishan granite barrier as an illustration example. As the distance between the fast water-conducting path (FWCP) and the disposal pit decreased from 80 m to 0, the nuclides' arrival time (Tt) in the biosphere decreased from 9000 to approximately 2000 years when the effects of the fault and the FWCP are considered. The maximum nuclide concentration (Cmax) increases from 0.0019 (350,000 years) to 0.0121 mSv/y (150,000 years), exceeding the limit of 0.01 mSv/y. In addition, as the permeability (equivalent hydraulic aperture) of the FWCP increased from 5.0 × 10−5 m to 1.0 × 10−4 m, the Tt of Cs-135 further decreases to about 15,000 years, and the Cmax increases to 0.0256 mSv/y (100,000 years), suggesting a significant reduction in the long-term performance of the geological barrier. These findings are helpful for site assessment of HLW repositories built in fractured granite.