Objective To investigate the role and underlying mechanism of heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) in ferroptosis of human gastric cancer MKN74 cells. Methods Bioinformatic analysis was performed to assess the correlation between HNRNPA1 and ferroptosis-related genes in TCGA gastric cancer dataset. Intracellular Fe²⁺ levels were measured by colorimetric assay, and ROS levels were measured using DCFH-DA fluorescent probe and fluorescence microscopy.Cell viability was determined by CCK-8 assay, and protein expression of SLC7A11 and GPX4 was detected by Western blot. Ferrostatin-1 (Fer-1) was used to inhibit ferroptosis and assess rescue effects. Results Bioinformatic analysis indicated that HNRNPA1 was highly expressed in gastric cancer tissues and positively correlated with SLC7A11. Knockdown of HNRNPA1 significantly increased intracellular Fe²⁺ accumulation and ROS levels, reduced cell viability, and downregulated SLC7A11 and GPX4 expression, while Fer-1 treatment partially reversed these effects. Conclusion HNRNPA1 knockdown promotes ferroptosis in MKN74 cells by downregulating the SLC7A11-GPX4 axis, leading to Fe²⁺ accumulation and ROS elevation. This study elucidates the regulatory role of HNRNPA1 in gastric cancer MKN74 cells ferroptosis and provides experimental evidence for potential HNRNPA1-targeted therapeutic strategies.