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Surfactant flooding can mobilize trapped oil and change the wettability of the rock to be more hydrophilic, which increases the oil recovery factor. However, the selection of surfactants is difficult in the case of high salinity conditions. In this work, we synthesized three novel anionic-nonionic surfactants based on widely used nonionic surfactant nonylphenol polyethoxylated (NPEO) and evaluated their efficiencies for enhanced oil recovery (EOR) in high salinity water (20% NaCl). The modified surfactants showed a decrease in interfacial tension (IFT) up to 10 times compared with the nonionic precursor. All surfactants had changed the wettability of rock to be more hydrophilic according to contact angle measurements. The effectiveness of surfactants was proved by spontaneous imbibition experiments, in which the synthesized surfactants showed a better displacement efficiency and increased oil production by 1.5–2 times. Filtration experiments showed an increase in oil recovery factor by 2–2.5 times in comparison with the nonionic NPEO. These promising results prove that the synthesis of new surfactants by modifying NPEO is successful and indicate that these novel surfactants have a great potential for EOR in high salinity reservoirs.