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<i>OsNRAMP5</i> is a pivotal gene involved in the uptake and transport of cadmium and manganese in rice plants. While the knockout of <i>OsNRAMP5</i> has significantly decreased cadmium accumulation in rice grains, its impact on the adaptability of <i>indica</i> hybrid rice and its paternal parent still needs to be more adequately explored. This study conducted a three-year field experiment with two of the <i>OsNRAMP5</i> knockout lines (<i>indica</i> hybrid rice LYDG-1 and its paternal parent DG-1) and their wild-type at four distinct locations in the middle reaches of the Yangtze River. Their adaptability was evaluated by cadmium and manganese accumulation, yield traits, and grain quality. The findings reveal that <i>OsNRAMP5</i> knockout lines, when grown in mildly and moderately Cd-contaminated paddies, exhibit significantly and stably lower cadmium and manganese accumulation compared with the wild-type. However, there were no significant differences in cadmium and manganese content between LYDG-1 and DG-1. Regarding yield traits, <i>OsNRAMP5</i> knockout lines did not show a significant reduction compared with the wild-type, except for DG-1 in soil with lower manganese content. For grain quality, the quality of the appearance of <i>OsNRAMP5</i> knockout lines significantly improved compared with the wild-type. However, the milling quality of DG-1 significantly reduced compared with the wild-type, while this negative impact for LYDG-1 was only observed in soils with lower manganese content. Overall, the <i>indica</i> hybrid rice with an <i>OsNRAMP5</i> knockout exhibits better adaptability than its paternal parent in the middle reaches of the Yangtze River. These findings offer valuable insights into the potential application and promotion of <i>OsNRAMP5</i> mutant rice varieties in the middle reaches of the Yangtze River.