Inductively couple plasma optical emission spectrometry (ICP-OES) is widely used to monitor elements in biological samples from marine organisms for ecological evaluations. Matrix effects (particularly those related to acid and salt type and concentrations) can present a barrier to the applicability of this instrumental method. To have a better understanding of these effects and to choose a suitable internal standard to correct for the signal variations, a procedure based on Principal Component Analysis (PCA) of the data from an axial-mode ICP-OES instrument with sequential detection was performed. Different from other published studies, it was found that ionic lines were more affected by matrix changes. Elements with high ionization energies and energy sums such as Cd and Zn showed a significant change for signal intensities and calculated concentrations due to the presence of acid, salt, and multielement matrix effects. It was observed that acid has a higher influence on the analyte signal as compared to the "salt-only" case. Furthermore, when several interfering elements were present in the sample, the matrix effect was either enhanced or reduced when compared with a solution containing only a single interfering element. Applicability of the proposed technique for the analysis of whale liver homogenate NIST certified material was investigated. The values of the corrected concentrations were in good agreement with the certified values, confirming the capabilities of the selected internal standards for compensation of matrix effects.