The aim of the present investigation was to develop a biosensor based on a quartz crystal nanobalance (QCN) for the detection of histidine (His). A thin layer of nickel was electrochemically deposited over the gold crystal electrode and exposed to H(2)O(2) to form nickel oxide. The composite electrode was then used to determine His. The frequency shifts were linear with respect to the concentration of His in solution. His can be measured in the range of 100-2000 mg L(-1). A lower limit of detection of 48 mg L(-1) and a sensitivity factor of 0.0307 Hz/mg L(-1) was obtained. Some possible interferences were checked for, and the performance of the sensor was found to be unaffected by any interference except for those from arginine, cysteine and NaH(2)PO(4). Principal component analysis (PCA) was used to process the frequency response data of the single piezoelectric crystal at various times, considering the different adsorption-desorption dynamics of His and the interfering compounds. Over 85% of the variance in the data was explained by two principal components. A score plot of the data for the first two PCs showed that the modified QCN yields favorable identification and quantification performances for His and the interfering compounds.