We found that the typical fluoroquinolone antibiotic enrofloxacin (ENR) and plasticizer di-(2-ethylhexyl) phthalate (DEHP) are often detected simultaneously and at high frequencies in the environment, but their combined exposure effects on soil animals are poorly understood. Here, oxidative stress, DNA damage and changes in digestibility of the earthworm were investigated to reflect the toxicological effects of single and combined exposure of DEHP and ENR on earthworms (Eisenia fetida). We found that the DEHP treatment group and the combined pollution treatment group showed significantly increased reactive oxygen species content of earthworms at 14 d and 28 d. ENR exposure alone had little effect on the antioxidant enzyme system, while DEHP and combined treatment showed a trend of inhibition and then activation. Addition of both pollutants caused a rise in the lipid peroxidation levels of earthworms. Malonaldehyde (MDA) was mainly scavenged by glutathione sulfur transferase (GST). ENR and DEHP caused more DNA damage to earthworm tissue than their combined pollution under the regulation of GST. Both single and combined pollution inhibited the digestive enzyme activity of earthworms, but the combined pollution had a stronger inhibitory effect. Cellulase, MDA and GST were the three most sensitive indicators on PCA. The toxicity was ENR + DEHP > DEHP > ENR according to the IBR index, and the combined toxicity showed a synergistic effect. The results showed that the combined pollution of phthalate esters and antibiotics in the actual environment was a significant ecological risk that deserves special attention.