Bacillus thuringiensis (Bt) is one of the used bioagents in insect pest control. Its toxicity is largely due to the insecticide endotoxins (crystalline (Cry) proteins) that act selectively on insects and nematodes. The efficiency of 20 of the most common Coleopteran-specific Cry proteins of Bt strains was tested against third instar-larvae of the red flour beetle Tribolium castaeum (Herbst.) (Coleoptera: Tenebrionidae). The primary screening results revealed that 11 Cry proteins (Cry8Ea, Cry8Fa, Cry1Ba, Cry8Ca, Cry1Fb, Cry1Ea, Cry1Ca, Cry55Aa, Cry9Da, Cry1Da, and Cry1Ia) were not toxic at all, 4 Cry proteins (Cry1Aa, Cry14Aa, Cry8Aa, and Cry7Ab) did not cause mortality but caused significant inhibition of growth, and 5 Cry proteins (Cry3Aa, Cry37Aa, Cry22Aa, Cry51Aa, and Cry3Ba) were toxic to T. castaneum larvae. The active 5 Cry proteins were used in the subsequent experiments. Five concentrations, being 0.25, 0.5, 1.0, 1.5, and 2.0 g Cry protein/10 g diet were used against the third instar larvae, and their mortalities were estimated. The LC50 values of Cry3Aa, Cry37Aa, Cry22Aa, Cry51Aa, and Cry3Ba were 0.46, 0.77, 1.25, 1.45, and 1.60 g/10 g, respectively. While the LT50 values of the same Cry proteins (for the concentration 2 g/10 g diet) were 1.50, 1.93, 2.29, 2.23, and 4.22 days, respectively. The results indicated that Cry3Aa was the most active one against T. castaneum larvae. The results of the sublethal study showed that the application of LC30 value of the active 5 Cry proteins reduced total eggs laid daily per female within 2 weeks, where, the percent decrease in egg numbers were 50.55, 38.56, 31.31, 23.20, and, 18.10% for Cry3Aa, Cry37Aa, Cry22Aa, Cry51Aa, and Cry3Ba, respectively. In addition, the hatchability rate of eggs, the larval, and pupal durations of T. castaneum decreased, while the pre-ovipositional period was prolonged. Furthermore, the larvae fed on a diet containing LC30 concentrations of Cry protein showed lower glycogen and lipid rates and generally lower protein content than the control larvae. When T. castaneum larvae were treated by Cry proteins, the level of digestive enzymes found in the midgut was decreased. The present findings indicated that Bt strains/Cry proteins had significant potential for controlling T. castaneum