Two new squaramide-based platinum(II) complexes C1 and C2 have been synthesized and fully characterized. Their photoresponse has been assessed and is discussed. A remarkable enhancement in the DNA binding activity has been observed for both complexes, up on irradiation. For C2, the release of Pt(II) provoked by its irradiation has been studied. The response of C2 has been found to be regulated by the presence of oxygen. In vitro cytotoxicity tests show an enhancement in the activity of complex C2 after selective irradiation under hypoxic conditions. Resulting Pt(II) species have been isolated and characterized by various analytical methods establishing this type of squaramido-based complexes as a proof of concept for new Pt(II) photocages.