Artificial tethering of INO80 at a genomic site enriched in R-loops results in turnover of R-loops in cis. Notably, removal of R-loops by overexpression of the RNA:DNA endonuclease RNAse H1 rescues the growth defects caused by INO80 depletion in PC3 cells, NRAS-dependent melanoma WM1361 cells and estrogen-dependent breast cancer MCF7 cells, while inhibition of the BER pathway sensitizes INO80-depleted cancer cells to lethality. Here, INO80 is linked to breast carcinoma.