The clinical application of disulfiram (DSF) in cancer treatments is hindered by its rapid degradation in the blood circulation. In this study, methoxy poly(ethylene glycol)- b-poly(lactide- co-glycolide)/poly(ε-caprolactone) (mPEG- b-PLGA/PCL) micelles were developed for encapsulation of DSF by using the emulsification-solvent diffusion method. Medium chain triglyceride (MCT) was incorporated into the mixed polymeric micelles to improve drug loading by reducing the core crystallinity. Differential scanning calorimetry (DSC) results implied that DSF is likely present in an amorphous form within the micelles, and is well dispersed. DSF is encapsulated within the core and the reservoir is stabilized by the hydrophilic shell to prevent rapid diffusion of DSF from the core. The DSF mixed micelles (DSF-MMs) showed good drug loading (5.90%) and a well-controlled particle size (86.4 ± 13.2 nm). The mixed micelles efficiently protected DSF from degradation in plasma, with 58% remaining after 48 h, while almost 90% of DSF was degraded after the same period for the DSF solution (DSF-sol), which was used as a control. The pharmacokinetics study showed that the maximum plasma concentration and bioavailability of DSF were improved by using the DSF-MMs (2 and 2.5 times that of the DSF-sol). The TIRs (tumor inhibition rates) of 5-FU, DSF-sol, and DSF-MMs were 63.46, 19.57, and 69.98%, respectively, implying that DSF-MMs slowed the growth of a H22 xenograft tumor model effectively.