Short interfering RNAs (siRNAs) are potent nucleic acid-based drugs designed to target disease driving genes that may otherwise be undruggable with small molecules. However, the potential of administering therapeutic siRNA in vivo is limited by poor pharmacokinetic properties, including rapid renal clearance and nuclease degradation. Nanocarriers have traditionally been explored as means to overcome these challenges, but they have intrinsic downsides such as dose-limiting toxicity and synthetic complexity. Backpacking on natural carriers such as albumin, which is present at high concentration and has a long half-life in serum, is an effective way to modify pharmacokinetics of biologic drugs that otherwise have poor bioavailability. In this work, we sought to develop albumin-binding aptamer-siRNA chimeras to improve the bioavailability of siRNA. We used a Systematic Evolution of Ligands through Exponential Enrichment (SELEX) approach to obtain RNA aptamers with modified bases that bind albumin with high affinity. We then fused the aptamers directly to an siRNA to generate the chimera structure. These aptamer-siRNA chimeras are stable in serum, exhibit potent gene knockdown capabilities in vitro, and display extended circulation time in vivo. We suggest that this albumin-binding aptamer-siRNA chimera approach is a promising strategy for drug delivery applications.