Half-light and half-matter exciton polaritons have demonstrated profound impacts on coherent quantum phenomena. Two-dimensional (2D) organic−inorganic perovskite semiconductors, exhibiting large exciton binding energy and spin-based behavior, are an excellent platform for the study of exciton polaritons at room temperature. However, the implementation of these fascinating coherent phenomena is still constrained by the lack of an understanding of the crucial polariton-polariton interaction effects. Here, an experimental observation of spin-dependent polariton-polariton interactions in a prototype 2D organic−inorganic perovskite microcavity by circularly polarization-resolved transient absorption (TA) measurements is reported. A power-dependent blue shift of the lower polariton bands with the same spin is clearly revealed, whereas the energy band of the polariton bands with the opposite spin is almost not changed. Spectacularly, it is found that the energy band blue shift mainly takes place before the spin depolarization, which provides accurate evidence for the spin-dependent polariton-polariton interactions. Furthermore, the strong coherent polariton-phonon coupling of perovskite microcavity has also been detected firstly in ultrafast TA dynamics. These results demonstrate that microcavity polaritons inheriting the matter properties from their excitonic constituents exhibit strong nonlinear interactions and pave the way for realizing coherent quantum phenomena at room temperature.