Twin-field (TF) quantum key distribution (QKD) is highly attractive because it can beat the fundamental limit of secret key rate for point-to-point QKD without quantum repeaters. Many theoretical and experimental studies have shown the superiority of TFQKD in long-distance communication. All previous experimental implementations of TFQKD have been done over optical channels with symmetric losses. But in reality, especially in a network setting, the distances between users and the middle node could be very different. In this paper, we perform a proof-of-principle experimental demonstration of TFQKD over optical channels with asymmetric losses. We compare two compensation strategies, that are (1) applying asymmetric signal intensities and (2) adding extra losses, and verify that strategy (1) provides much better key rate. Moreover, the higher the loss, the more key rate enhancement it can achieve. By applying asymmetric signal intensities, TFQKD with asymmetric channel losses not only surpasses the fundamental limit of key rate of point-to-point QKD for 50 dB overall loss, but also has key rate as high as 2.918 × 10−6 for 56 dB overall loss. Whereas no keys are obtained with strategy (2) for 56 dB loss. The increased key rate and enlarged distance coverage of TFQKD with asymmetric channel losses guarantee its superiority in long-distance quantum networks.