To improve the efficiency of wireless data communications, new physical-layer transmission methods based on known-interference cancellation (KIC) have been developed. These methods share the common idea that the interference can be cancelled when the content of it is known. Existing work on KIC mainly focuses on single-hop or two-hop networks, with physical-layer network coding (PNC) and full-duplex (FD) communications as typical examples. This paper extends the idea of KIC to general multi-hop networks, and proposes an end-to-end KIC (E2E-KIC) transmission method together with its MAC design. With E2E-KIC, multiple nodes in a flow passing through a few nodes in an arbitrary topology can simultaneously transmit and receive on the same channel. We first present a theoretical analysis on the effectiveness of E2E-KIC in an idealized case. Then, to support E2E-KIC in multi-hop networks with arbitrary topology, we propose an E2E-KIC-supported MAC protocol (E2E-KIC MAC), which is based on an extension of the Request-to-Send/Clear-to-Send (RTS/CTS) mechanism in the IEEE 802.11 MAC. We also analytically analyze the performance of the proposed E2E-KIC MAC in the presence of hidden terminals. Simulation results illustrate that the proposed E2E-KIC MAC protocol can improve the network throughput and reduce the end-to-end delay.