The aim of this work was to evaluate the change in the quality of litchi juice treated by DMDC combined with Nisin during storage of 4 °C. Results found that addition of 250 mg/L of DMDC combined with 100 IU/mL of Nisin can ensure the microbiological safe of litchi juice during storage at 4 °C. Compare with heat treatment (95°C, 1 min), the treatment of DMDC combined with Nisin can retain a more value of sensory attributes, but a more loss in the content of total phenolics, ascorbic acid, and antioxidant capacity was observed during storage at 4 °C because of the ineffectiveness of DMDC and Nisin to the oxidase of litchi juice. Moreover, no significant change (P > 0.05) was observed in the value of L∗, a∗, b∗, and △E in the heat-treated litchi juice, and yet the litchi juice treated by DMDC and Nisin gradually turned into light red at the end of storage because of the oxidation of phenolics by residual POD in the litchi juice, which resulted in a significant changes (P < 0.05) in the value of L∗, a∗, b∗, and △E in the litchi juice. This study would provide technical support for commercial application of DMDC combined with Nisin in litchi juice processing.