The Egyptian cotton leafworm, Spodoptera littoralis (Boisduval) , is known as an important and highly polyphagous pest species worldwide. The objective of the present study was to evaluate synergistic effects of Bacillus thuringiensis subsp. kurstaki and NucleoPolyhedroVirus (SpliMNPV) on the 5-day-old larvae (2nd instars) of S. littoralis under laboratory conditions. To do this, the larvae of S. littoralis were fed on the treated artificial diet containing only one or combination of Bt (8.31×105, 2.78×107, 9.69×108 spore mL-1) and SpliMNPV (5.26×10, 7.03×102, 9.39×103 OB mL-1). According to the results, the mortality rate for most of the Bt-SpliMNPV combinations (different concentrations) was higher than that in the treatments containing only one of the studied biocontrol agents. The Bt-SpliMNPV combinations showed different types of interactions, including synergistic, additive, or antagonistic effects. The treatment containing 8.31×105 spore mL-1 of Bt and 5.26×10 OB mL-1 of the SpliMNPV was interpreted as synergism effect, as the real mortality (72.41±12.43%) was significantly more than the expected (48.28%). In addition, application of the Bt-SpliMNPV combinations could significantly increase larval and pupal periods, and reduce pupation, pupal weight and the adult emergence rate compared to the control and treatments containing only one of Bt or SpliMNPV. Finally, it could be concluded that co-application of Bt and SpliMNPV can enhance economic and efficient control of S. littoralis.