Preformed particle gel (PPG) treatment is now one of the most effective remediation techniques for conformance controlling and selective plugging of high-water flow conduits in mature water-flooded oil reservoirs. Recognizing the intrinsic properties of PPGs, e.g., the swelling ratio, in reservoir condition is of prime importance to the optimization of their performance as plugging agents. In this study, the classical and three-level full factorial experimental design methods are joined with laboratory measurements to investigate the swelling ratio dependency of a new class of enhanced PPGs at different brine salinities and reservoir temperatures. To cover severe reservoir conditions, the reservoir temperature from 298 to 418 K and brine salinity from 0 to 225,000 ppm were considered during the laboratory measurements. The results show that the swelling ratio decreases by rising water salinity. Moreover, the swelling ratio rises by increasing reservoir temperature up to 380K and then starts to decrease. The factor screening illustrates that the swelling ratio is more dependent on salinity than the reservoir temperature in low salinity solutions, while is less dependent on salinity in high salinity solutions. In addition, a precise mathematical model was developed to predict the swelling ratio of PPGs in a wide range of salinities and temperatures. The results of this study present a practical insight into the swelling-related behavior of the PPGs at reservoir conditions.