▪Increased toxicity and reduced tumourigenesis in drug (Tamoxifen) resistant BC cells▪Gas plasma re‐sensitized BC cells to Tamoxifen by reversing expression of BAG1, CD24 and HDAC4 genes▪Decreased colony formation, and tumourigenesis in siMX1 and HOXC6 ORF transfected cells▪Altered drug resistance status in BC cells by modification of XRCC, SOX9 and SULT1A1 expression▪ROS scavenger inhibited the gas plasma effects. Here, HDAC4 is linked to breast cancer.