Recent evidence suggests that small non-coding RNAs or microRNA (miRNA)s encapsulated in exosomes represent an important mechanism of communication between the cells. Exosomal miRNAs play an important role in oncogenesis via stimulating cell to cell communication and facilitating metastasis in cancers. Despite progressive advances, current methods for exosomal miRNA detection most rely on labor intensive sequencing approaches which are often prone to amplification bias and require costly and bulky equipment. Herein, we report an electrochemical approach for detection of cancer-derived exosomal miRNAs in human serum samples by selectively isolating the target miRNA using magnetic beads pre-functionalized with capture probes and then directly absorbing the targets onto the gold electrode surface. The level of adsorbed miRNA is detected electrochemically in the presence of the [Fe(CN)6]4-/3- redox system. This method enabled an excellent detection sensitivity of 1.0 pM with a relative standard deviation (%RSD) of <5.5% in cancer cells and serum samples (n = 8) collected from patients with colorectal adenocarcinoma. We believe that our approach could be useful for the quantification of exosomal miRNA in clinical samples.