Despite numerous organic semiconductors being developed during the past decade, C70 derivatives are predominantly used as electron acceptors in efficient polymer solar cells (PSCs). However, as-prepared C70 mono-adducts intrinsically comprise regioisomers that would mask individual device performances depending on the substituent position on C70. Herein, we separate the regioisomers of C70 mono-adducts for PSC applications for the first time. Systematic investigations of the substituent position effect using a novel symmetric C70 mono-adduct ([70]NCMA) and a prevalent, high-performance one ([70]PCBM) reveals that we can control the structures of the blend films with conjugated polymers and thereby improve the PSC performances by regioisomer separation. Our approach demonstrates the significance of exploring the best-matching regioisomer of C70 mono-adducts with high-performance conjugated polymers, which would achieve a remarkable progress in PSC devices.