Hydrogen peroxide (H2O2) is upregulated in tumour microenvironments and may contribute to effects on metastatic cancer cells. This study demonstrates that treatment of lung carcinoma and melanoma cells with H2O2 for 14 days results in an induction of anoikis resistance and growth in an anchorage-independent condition. H2O2 exposure increased the Cav-1 (caveolin-1) level through an increase of Cav-1 mRNA with minimal effect on protein degradation. Upregulation of Cav-1 induced anoikis resistance and facilitated growth in a detached manner. The findings show a novel role of hydrogen peroxide in the regulation of metastatic potential of cancer cells.