The aim of this study was to measure the secretion of interleukin (IL)-8 and -10 during an elicited immune response following sublethal doses of hypericin-mediated photodynamic therapy (HY-PDT) in experimental models of residual colon cancer cells in vitro. Investigations were performed on the cancer cell lines SW480 and SW620. Each cell line was exposed to 3 different concentrations of the photosensitizer HY and various doses of irradiation. The cell metabolic activity using an MTT assay was performed and then the measurement of IL-8 and IL-10 secretion was achieved using the Bio-Plex ProTMAssay. There was a statistically significant amplification of IL-8 secretion during HY-PDT in the SW620 cell line (at 1 J/cm2: P = .01, 5 J/cm2: P = .002, and 10 J/cm2: P = .025) and a statistically significant decrease in IL-8 during HY-PDT in the SW480 cell line (at 1 J/cm2: P = .05, 5 J/cm2: P = .035, and 10 J/cm2: P = .035). No statistically significant differences in IL-10 concentration were found following HY-PDT in the SW480 (at 1 J/cm2: P > .4, 5 J/cm2: P = .1, and 10 J/cm2: P = .075) or in the SW620 cell line (at 1 J/cm2: P > .4, 5 J/cm2: P > .4, and 10 J/cm2: P > .4). HY-PDT can both eliminate and control a primary tumor via cytotoxic effects, and at sublethal doses, it can affect IL release by colon cancer cells. In this experiment, this influence depended on the level of tumor cell metastatic activity.