Purpose: To develop a realistic model for the dosimetric distribution and to evaluate biological effective dose (BED) of Praseodymium‐142 (Pr‐142) and Yttrium (Y‐90) glass microspheres in blood vessel within tumor for treating hepatocellular carcinoma (HCC). Methods: Blood vessels filled with uniformly distributed microspheres were modeled and positioned along the central axis of the tumor. Cylindrical blood vessels had diameters ranging from 25.0 to 75.0 μm, while tumor radii were varied from 0.2 to 1.0 cm, based on average values reported in the literature. Physical dose distributions due to a single blood vessel were simulated using Monte Carlo (MCNPX2.6) for large combinations of blood vessel and tumor sizes. HCC doubling times (DT) ranging from 17 to 720 days were used as a parameter in the BED calculations. To quantify the BED coverage throughout the entire tumor volume, a BED volume histogram (BEDVH) was calculated for each nuclide. Results: The physical dose distribution for both nuclides was comparable, e.g. dose per decay of 1.95 × 10−12 Gy and 2.36 × 10−12 Gy were obtained for Pr‐142 and 90‐Y point source at the same point, respectively. Pr‐142 distribution yielded higher BED coverage of the tumor volume for all DT, blood vessel sizes, and tumor sizes. The differences were higher for fast proliferating tumors and smaller tumor and blood vessel sizes, e.g. for 17 days DT, 20 μm blood vessel diameter and 0.2 cm tumor radius, BED coverage of 150 Gy was 48.7 % higher for Pr‐142. Conclusion: Blood vessels modeled within tumors made possible the quantification of the dose range due to a single embolized blood vessel. From BEDVH evaluation it appeared that the biological effectiveness throughout the tumor was sensiμtive to the radionuclide used, tumor sizes, and blood vessel sizes. The work was partially supported by a Ralph E. Powe Junior Faculty Enhancement Award provided by Oak Ridge Associated Universities.