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Abstract The role of H i content in galaxy interactions is still under debate. To study the H i content of galaxy pairs at different merging stages, we compile a sample of 66 major-merger galaxy pairs and 433 control galaxies from the Sloan Digital Sky Survey IV (SDSS-IV) MaNGA IFU survey. In this study, we adopt kinematic asymmetry as a new effective indicator to describe the merging stage of galaxy pairs. With archival data from the HI-MaNGA survey and new observations from the Five-hundred-meter Aperture Spherical radio Telescope (FAST), we investigate the differences in H i gas fraction (f H I), star formation rate (SFR), and H i star formation efficiency (SFEH I) between the pair and control samples. Our results suggest that the H i gas fraction of major-merger pairs on average is marginally decreased by ∼15% relative to isolated galaxies, implying mild H i depletion during galaxy interactions. Compared to isolated galaxies, pre-passage paired galaxies have similar f H I, SFR, and SFEH I, while pairs during the pericentric passage have weakly decreased f H I (−0.10 ± 0.05 dex), significantly enhanced SFR (0.42 ± 0.11 dex), and SFEH I (0.48 ± 0.12 dex). When approaching the apocenter, paired galaxies show marginally decreased f H I (−0.05 ± 0.04 dex), comparable SFR (0.04 ± 0.06 dex), and SFEH I (0.08 ± 0.08 dex). We propose that the marginally detected H i depletion may originate from the gas consumption in fueling the enhanced H2 reservoir of galaxy pairs. In addition, new FAST observations also reveal a H i absorber (N H I ∼ 4.7 × 1021 cm−2), which may suggest gas infalling and the triggering of active galactic nuclei activity.