In this work, we reported the control size and shape dependent cellular interactions of ZnO nanoparticles ranging from tiny nanodisks to nanorods, with carcinoma cells. These particles were synthesized through the wet chemical synthesis approach. Size and shape of the ZnO nanoparticles were tuned by varying the concentration of Igapal CO50. Size and shape dependent interactions were investigated with human carcinoma cells (K562, a Leukaemia Cancer Cells) without attaching any anticancer drugs and the results manifest that the size, shape and physical properties of ZnO nanoparticles are preferentially the critical factors in interactions and killing the cancer cells when no anticancer drugs were used. ZnO nanoparticles are used of aspect ratio from 1.3 to 5.5. Interaction and killing of carcinoma cells depend on the extent of defects and on the electro paramagnetic behavior of the ZnO nanoparticles. Further, Raman and EPR studies revealed that the size dependent phonon localization of oxygen defects of ZnO control the formation of singlet oxygen on interactions with cancer cells and regulate the anticancer effects of ZnO nanoparticles even in the absence of drugs. ZnO NPs with low aspect ratio is more vigorous in killing the carcinoma cells.