A five-compartmental biokinetic model of I-131 radioiodine based on in-vivo gamma camera scanning results was developed and successfully applied to nine thyroid cancer patients who were administered 1,110 MBq I-131 in capsules for the residual thyroid gland ablation. The I-131 solution activity among internal organs was analyzed via the revised biokinetic model of iodine recommended by the ICRP-30 and -56 reports. Accordingly, a five-compartmental (stomach, body fluid, thyroid, whole body, and excretion) model was established to simulate the metabolic mechanism of I-131 in thyroid cancer patients, whereas the respective four simultaneous differential equations were solved via a self-developed program run in MATLAB. This made it possible to provide a close correlation between MATLAB simulation results and empirical data. The latter data were collected through in-vivo gamma camera scans of nine patients obtained after 1, 4, 24, 48, 72, and 168 hours after radioactive I-131 administration. The average biological half-life values for the stomach, body fluid, thyroid, and whole body of thyroid cancer patients under study were 0.54±0.32, 12.6±1.8, 42.8±5.1, and 12.6±1.8 h, respectively. The corresponding branching ratios I12, I23, I25, I34, I42, and I45 as denoted in the biokinetic model of iodine were 1.0, 0.21±0.14, 0.79±0.14, 1.0, 0.1, and 0.9, respectively. The average values of the AT dimensionless index used to verify the agreement between empirical and numerical simulation results were 0.056±0.017, 0.017±0.014, 0.044±0.023, and 0.045±0.009 for the stomach, thyroid, body fluid + whole body, and total, respectively. The results obtained were considered quite instrumental in the elucidation of metabolic mechanisms in the human body, particularly in thyroid cancer patients.