Several factors influence the IFT of oil and formation water. These factors are rooted in the complex composition of oil, presence of different salts in water, water salinity, temperature, and pressure of reservoir. In the first part of this paper, effect of salinity on IFT between brine and an Iranian live oil sample has been studied experimentally. It is observed that IFT increases almost linearly with brine concentration. Also, linear increasing behavior of IFT with respect to pressure is obviously seen. Then, using thermodynamic properties such as surface excess concentration, chemical potential, chemical activity, and activity coefficient, results were analyzed and observed effect of salinity and pressure were justified thermodynamically. In the second part, the effect of asphaltene on IFT reduction has been studied. In previous works, the investigators extracted resin and asphaltene and then examined their effects on IFT in the absence of other fractions of oil phase. We believe that all fractions play a role in this phenomenon so, in this paper, the effect of natural surfactants of oil phase on IFT has been investigated in presence of all fractions of oil. Hence, SARA test was performed on all samples. Then, IFT between oil samples and brine were measured using captive drop instrument at 25 °C and 3000 psia. Results showed that neither asphaltene content nor asphaltene/resin ratio is a good indicator for effect of asphaltene on IFT, whereas colloidal instability index could be a useful tool to predict asphaltene effect on IFT.