As an organophosphate ester (OPE), triphenyl phosphate (TPhP) has been frequently detected in aquatic environments, and its environmental risk has been widely studied. The gills and intestines are the most important part of the mucosal immune barrier in fish as the first line of defense against the invasion of harmful substances. TPhP is more abundant in the gill and intestine of fish. However, knowledge of the toxic effects and potential mechanisms of TPhP on the intestine and gill is limited. Herein, the adverse effects of TPhP (0.01, 0.1 and 1 mg/L) on the gills and intestines of zebrafish after 75 days of exposure were investigated from the perspectives of histology, oxidative stress and immune level. The histological results of exposed zebrafish showed that TPhP caused significant damage to gills and intestines. TPhP significantly increased the activities of the antioxidant enzymes catalase (CAT) and glutathione s-transferase (GST), inducing oxidative damage to lipids, proteins, and DNA. Meanwhile, the immune function of the gills and intestines was significantly influenced by TPhP, as evidenced by the upregulation of the expression of interleukin-1β (IL-1β) and interleukin-6 (IL-6), upregulation of the content of complement 3 (C3) and complement 4 (C4), and downregulation of the activity of lysozyme (LZM) and the content of immunoglobulin M (IgM). Oxidative stress and the immune response were more severe in the gills. These findings indicate that TPhP, a typical OPE, caused tissue damage in aquatic organisms by inducing oxidative stress and immune damage and has strong environmental toxicity.