Ultrafast linear selective isomerization-hydroformylation (ISO-HF) tandem reaction under mild conditions remains a challenge. Herein, a novel tetraphosphite ligand (TBTP) and its application in ISO-HF of C4 Raffinate were reported. Based on a biphenol-2,2′,6,6′-tetraol with sterically demanding tert-butyl substituents, TBTP can be readily prepared by the reaction of biphenyl phosphorchloridite and tetraol in kilogram scale. The structural and coordinating features of this ligand and its rhodium complex were studied by XRD, NMR and DFT calculations. This tetraphosphite ligand showed high turnover frequencies and regioselectivities in the rhodium-catalyzed ISO-HF of trans-, cis-2-butene. Such hydrolytically stable ligand was successfully applied in the ISO-HF of etherified C4 feed under a mild condition (65 °C, 7 bar syngas, TOF up to 1574 h⁻¹, ∼95% linear selectivity). An over-14-day durability test that was operated in two 5-L continuously stirred-tank reactors (CSTRs) in series delivered 79 kg n-valeraldehyde for the manufacture of C10 plasticizer DPHP.