The hypothesis of our study was that waterborne Zn exposure evoked phospholipids (PL) biosynthesis to compensate for the loss of membrane integrity, and the pathways of oxidative stress and endoplasmic reticulum (ER) stress mediated the Zn-evoked changes of PL biosynthesis. Thus, we conducted RNA sequencing to analyze the differences in the intestinal transcriptomes between the control and Zn-treated P. fulvidraco. The 56-day Zn exposure increased the intestinal Zn accumulation, and mRNA levels of 816 genes were markedly up-regulated, while that of 263 genes were down-regulated. Many differentially expressed genes in the pathways of PL biosynthesis and protein processing in ER were identified. Their expression profiles indicated that waterborne Zn exposure injured protein metabolism, induced PL biosynthesis caused oxidative stress and ER stress, and activated the unfolded protein response. Then, using the primary enterocytes, we identified the mechanism of oxidative and ER stress mediating Zn-induced PL biosynthesis, and indicated that the activation of these pathways constituted adaptive mechanisms to reduce Zn toxicity. Our study demonstrated that Zn exposure via the water increased Zn accumulation and PL biosynthesis, and that oxidative stress and ER stress were interdependent and mediated the Zn-induced PL biosynthesis of the intestine in the freshwater teleost.