Streptococcal collagen-like protein 1 (Scl1) is a virulence factor on the surface of group A Streptococcus (GAS). We have previously reported that several Scl1 proteins derived from various M-type GAS strains, including M41, can bind to low-density lipoprotein but Scl1 protein derived from M6-type GAS strain can not. Here, we demonstrated that recombinant protein, designated C176, derived from Scl1.41 of GAS M41-type strain also binds both plasma and purified high-density lipoprotein (HDL). Next, we determined that intact non-collagenous region of C176 was necessary and sufficient for HDL binding. C176-HDL interaction could be eliminated by the presence of low concentrations of the nonionic detergent, Tween 20, suggesting hydrophobic character of this interaction. We finally showed that whole GAS cells expressing native Scl1.41 protein absorbed HDL from human plasma in the absence of Tween 20 but M6-type GAS cells did not. Altogether, our results add further evidence to the importance of GAS-lipoprotein binding.