Targeted protein degradation technology can achieve the modulation of undruggable proteins. Abnormal activation of cyclins can promote tumorigenesis and tumor progression. However, cyclins regard to be undruggable with no small-molecule binders had been released. Here, we utilize hydrophobic tag (HyT)-based small-molecule degraders induced degradation of cyclin T1 and its corresponding kinase partner CDK9. We describe the discovery of a series of novel dual degraders of CDK9-cyclin T1. LL-CDK9-12 demonstrated the most potent and selective degradation ability, with DC50 values of 0.362 μM against CDK9 and 0.680 μM against cyclin T1. In prostate cancer cells, LL-CDK9-12 showed enhanced anti-proliferative activity than its parental molecule SNS032. Moreover, LL-CDK9-12 suppressed the downstream signaling of CDK9 and AR efficiently. Altogether, LL-CDK9-12 was an effective dual degrader of CDK9-cyclin T1 and could be useful in studying the unknown function of CDK9-cyclin T1. Our data also suggest that HyT-based degraders could be used as a strategy to induce the degradation of protein complexes that containing undruggable proteins such as cyclins.