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 first 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.Quantum key distribution (QKD) enables remote users to share secret keys with information-theoretic security [1,2]. However, due to the unavoidable losses of optical channels, there exists a fundamental limit on the achievable secret key rate of long distance QKD. Without using quantum repeaters, the upper bound (also called repeaterless bound in this paper) of the secret key rate of QKD scales linearly with the channel transmittance η [3,4]. Remarkably, a new type of QKD, called twin-field (TF) QKD, has been proposed [5] and can practically overcome the repeaterless bound. In TFQKD, like in the measurement-deviceindependent (MDI) QKD [6], two users (Alice and Bob) send two coherent states to an un-trusted intermediate node, i.e. Charlie, who performs the measurement. Because TFQKD employs single photon interference, rather than two-photon interference in MDIQKD, the secret key rate of TFQKD scales as √ η, allowing for unprecedented distance coverage. Plenty of variations and security analysis of TFQKD [7-12] have been studied, followed by multiple experimental demonstrations [13][14][15][16]. More recently, TFQKD has been successfully implemented over more than 500 km fibers [17,18]. It has been shown that TFQKD is one of the most promising and practical solutions to long distance QKD. However, all the above mentioned studies only consider TFQKD over optical channels with symmetric losses between each of the users and intermediate node, and let Alice and Bob use identical sets of operations in preparing their signals. However, this assumption on channel symmetry is seldom true in reality. TFQKD over asymmetric channels is important not only for practical po...