The aim of the study was to investigate the influence of discrete structural differences in synthetic porphyrins on the antineoplastic effect induced in myelocitic cell line K562 after experimental photodynamic therapy procedure. For this study, we used 5,10,15,20-tetra(1-naphthyl)porphyrin, 5,10,15,20-tetra(4-sulfonatophenyl)porphyrin and their Zn complexes. For all these compounds, the following photodynamic therapy parameters were optimized: cell concentration, dye loading concentration, loading time and irradiation procedure. The non-toxic doses of porphyrins were different according to their structure: for 5,10,15,20-tetra(1-naphthyl)porphyrin compounds, the dose was of 10 μg.mL-1, and for 5,10,15,20-tetra(4-sulfonatophenyl)porphyrin compounds, the dose was 20 μg.mL-1. Cell functionality was assessed as membrane integrity, viability, and number of metabolically active cells. Photodynamic cell degradation kinetics showed that during irradiation tumor cells are actively destroyed, in contrast to unloaded cells. K562 cells loaded with the above-mentioned compounds and subjected to irradiation, displayed lower proliferative capacity compared to the control, for a period of 72 h after irradiation. The proliferative capacity of K562 cell line was more strongly inhibited by the 5,10,15,20-tetra(1-naphthyl)porphyrin family of compounds than by the 5,10,15,20-tetra(4-sulfonatophenyl)porphyrin family. The tested synthetic porphyrins showed effective antineoplastic activity against K562 leukemia cells in our in vitro photodynamic therapy experimental model.