Photodynamic therapy (PDT) is a promising approach for cancer treatment; however, the clinical application of many photosensitizers is limited by poor aqueous solubility, unfavorable biodistribution, and insufficient tumor accumulation. In this study, we investigated whether PEGylation of the photosensitizer Photomed could improve its physicochemical properties and in vivo photodynamic therapeutic efficacy while preserving its intrinsic photochemical activity. A PEG-conjugated Photomed (Photomed-PEG) was synthesized and evaluated using singlet oxygen generation assays, cellular uptake analysis, and in vitro phototoxicity studies. The in vivo biodistribution and antitumor efficacy of Photomed-PEG were examined in an A549 tumor-bearing mouse model. PEGylation significantly improved the aqueous solubility of Photomed while maintaining singlet oxygen generation and minimal dark toxicity. Photomed-PEG also showed enhanced tumor accumulation and reduced nonspecific retention compared with non-PEGylated Photomed. These favorable pharmacokinetic properties resulted in stronger photodynamic antitumor effects, demonstrated by significant tumor growth suppression after light irradiation. Importantly, no significant body weight loss or histopathological abnormalities in major organs were observed, indicating a favorable safety profile. These findings suggest that PEGylation is an effective strategy to improve photosensitizer delivery and enhance PDT efficacy for solid tumor therapy.