Here, we report a facile molecular engineering approach with alkylthio and fluorine atom modified the conjugated side chain of quinoxaline-based polymer, namely DTFFQx-TS, which afforded lower highest occupied molecular orbital energy level and enhanced interchain interactions. The conventional devices based on DTFFQx-TS: ITIC exhibited the power conversion efficiency (PCE) of 5.26% with a remarkably high open circuit voltage (V-oc) of 0.99 V. This work not only provides a newly efficient candidate of quinoxaline acceptor block modified with fluorinated conjugated side chain, but also achieves high V-oc copolymers for polymer solar cells via the synergistic effect of fluorination and side chain engineering strategies.