Development of chemoresistance is a significant restriction on the success of cancer treatment. Combination chemotherapy and drug delivery nanosystem are two promising strategies to overcome this limitation. Administration of two or more anticancer drugs at the same time can promote synergistic effect and suppress drug resistance through distinct mechanisms of action. Drug delivery nanosystem, on the other hand, improves delivery, efficacy and safety of drugs, and also can escape from some mechanisms of drug resistance. In this study we prepared drug delivery nanosystems from copolymers of lactic acid (PLA) and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS). The nanosystems incorporated with folic acid as targeting agent were used to load curcumin (Cur) and paclitaxel (PTX) contemporaneously and denoted as (Cur + PTX)-PLA-TPGS-Fol. The results showed that (Cur + PTX)-PLA-TPGS-Fol nanoparticles has average size range of 100–200 nm depending on the ratio between PLA and TPGS. Loading efficacy of the two drugs was about 35%–83% with the highest encapsulation efficiency belonged to the system with the highest ratio of PLA. All of the prepared nanosystems with single drug or in combination exhibited strong cytotoxicity to cancer cells, but the combination was more effective in case of A549 cancer cell line. These results showed that our combination of Cur and PTX in our drug delivery nanosystem can be a promising candidate for cancer treatment.