A single-channel audio source separation algorithm based on the matching pursuit (MP) technique with content-adaptive dictionaries (CAD) is proposed in this work. The proposed MP-CAD algorithm uses content-dependent atoms that capture inherent characteristics of audio signals effectively. As compared with previous methods based on spectral decomposition and clustering in the time-frequency domain, the MP-CAD algorithm projects the time-domain audio signals onto a subspace spanned by content-adaptive atoms efficiently for their concise representation and separation. The effectiveness of the MP-CAD algorithm in audio signal approximation and single-channel source separation is demonstrated by computer simulation.