This paper presents a comparative experimental and numerical study of the heat transfer and pressure loss in a swirl multi-pass channel with tangential jet slots, and another baseline multi-pass channel with 180-deg U-bends as a comparison baseline has also been investigated. The tangential jets can induce large-scale swirling flows and significantly enhance the connective heat transfer. The swirl multi-pass channel can be considered as an effective internal cooling strategy for the gas turbine blades. Transient liquid crystal thermography is used to obtain the detailed heat transfer distribution on the internal surfaces of the multi-pass serpentine channels. The heat transfer patterns in the swirl multi-pass channel are quite different from those of the baseline multi-pass channel. Circumferentially, the three heat transfer surfaces, i.e., the bottom, top and side surfaces of the two multi-pass serpentine channels, have roughly similar trend along the flow direction and reach the peak values after the U-bends and jet injections, respectively. Compared with the baseline multi-pass channel, the experimental globally averaged Nusselt number ratios of the last two passes in the swirl multi-pass channel can be increased by up to 82.9%, 104.8%, and 124.6% for the Reynolds numbers 20,000, 40,000, and 60,000, respectively. The differences of globally averaged Nusselt number ratios between the two kinds of multi-pass serpentine channels gradually increase with the Reynolds numbers, which means that the swirl multi-pass channel has higher heat transfer enhancement capability at a higher Reynolds number. The circumferentially uniform heat transfer characteristic of swirling flow also performs well in this study. The high and circumferentially uniform heat transfer is mainly due to the large-scale swirling flow induced by the tangential slots. In more detail, the large-scale swirling flow impinges onto the surface and further induces high tangential velocity near the wall, which destroys the boundary layer flow and thus improves the heat transfer rates at the wall. However, the notable pressure loss of the swirl multi-pass channel should be further controlled reasonably, which is about 5.4 times that of the baseline multi-pass channel. As supplements to the experiments, three-dimensional numerical computations provide more insights into the turbulent flow structure in the two kinds of multi-pass serpentine channels.