Metastases in the liver frequently grow as scattered tumor nodules which neither can be removed by surgical resection nor focally ablated. Previously, we have proposed a novel technique based on irreversible electroporation which may be able to simultaneously treat all nodules in the liver while sparing healthy tissue. The proposed technique requires increasing the electrical conductivity of healthy liver by injecting a hypersaline solution through the portal vein. Aiming to assess the capability of increasing the global conductivity of the liver by means of hypersaline fluids, here it is presented a mathematical model which estimates the NaCl distribution within the liver and the resulting conductivity change. The model fuses well-established compartmental pharmacokinetic models of the organ with saline injection models employed for resuscitation treatments and it considers changes in sinusoidal blood viscosity due to the hypertonicity of the solution. Here it is also described a pilot experimental study in pigs in which different volumes of NaCl 20% (from 100 to 200 ml) were injected through the portal vein at different flow rates (from 53 to 171 ml/min). The in vivo conductivity results fit those obtained by the model, both quantitatively and qualitatively, being able to predict the maximum conductivity with a 14.6% average relative error. The maximum conductivity value was 0.44 S/m which corresponds to increasing four times the mean basal conductivity (0.11 S/m). The results suggest that the presented model is well suited for predicting on liver conductivity changes during hypertonic saline injection.