Melanoma is a malignant skin tumor that arises during the malignant transformation of melanocytes, and due to its aggressiveness and metastatic nature, it is the deadliest form of skin cancer. Conventional strategies in cancer treatment such as radiotherapy, chemotherapy, and biological therapy often cause side effects and are not able to overcome the problem of tumor resistance and hypoxia in the tumor microenvironment. One of the solutions is photodynamic therapy (PDT), a form of minimally invasive and clinically approved phototherapy. PDT is based on the interaction of light, photosensitizer, and oxygen, whereby a photochemical reaction occurs and the generation of reactive oxygen species is generated, which then causes the death of tumor cells, damages tumor blood vessels, and stimulates the immune response. The aim of this work was to test the effectiveness of porphyrins conjugated with lipophilic chains of different lengths, where two have N-oxidized and two N-methylated pyridyl groups on meso position. The cell uptake of porphyrins at different time points was determined by measuring the fluorescence intensity, fluorescence microscopy was used to examine the localization of porphyrins inside melanoma cell line, and the cytotoxicity of porphyrins was determined under normoxia and hypoxia using the MTT proliferation test. The results showed that the largest amount of the porphyrins was found in the cells after 6 h of incubation, and in larger amount in fibroblasts (HDF) in comparison to melanoma cell line (MeWO). Also, it was shown that porphyrins enter the cells in larger quantities at 37 ℃, which could indicate the entry of porphyrins by active transport into the cells. The results of the MTT test showed the potential selectivity of porphyrins for melanoma cells (MEWO) and show that porphyrins do not show dark toxicity in concentration up to 10 μM. The results of previous tests were also confirmed, showing that the higher lipophilicity of the compounds results in better cellular uptake and that N-oxidized compounds potentially work better in hypoxia