The oxygen evolution reaction (OER) with large overpotential is the bottleneck of the whole water electrolysis process. NiFe layered double hydroxide (NiFe-LDH) represent one of the potential catalysts for OER in alkaline media. For the LDH, it was well established that both adsorption evolution mechanism and lattice oxygen mechanism could appear at a single site, but Ni-OOOO-Fe species would provide a different OO path mechanism at dual-O sites due to the complexity and diversity of LDH surface. Here, using first-principles study, tetra-oxygen path mechanism (t-OPM) was proposed to investigate the OER performance of NiFe-LDH by considering surface 2O were as active sites (O_ac) and other O as environment O (O_ev) with different exposed degrees (0–6). It was found that the optimal performance of the NiFe-LDH surface could be achieved when 2 ∼ 4 O_ev were exposed under the explored mechanism in different paths (path 1 and path 2) with overpotential η = 0.07 ∼ 0.35 V, and path 1 was slightly better than path 2. At the same time, the solvation effect (SE) was used to study the effect on the OER performance, the results showed that SE had a little influence on the case of 2 ∼ 4 O_ev exposed while had a large effect on the other cases. The detailed analysis of the electronic structure showed a smaller difference Δε between the energy Fe-3d band center and O_ac-2p, which imply the stronger the interaction between them. Thus, the t-OPM was feasible in OER on NiFe-LDH. It was anticipated that our work could provide a fresh perspective on the understanding of the excellent OER performance of LDH in alkaline environment, which was complementary to the traditional mechanism to some extent.