One of the major applications (40% in Europe) of plastic is packaging, which is often printed to display required information and to deliver an attractive aesthetic for marketing purposes. However, printing ink can cause contamination in the mechanical recycling process. To mitigate this issue, the use of surfactants in an alkaline washing process, known as de-inking, has been employed to remove printing ink and improve the quality of recyclates. Despite the existence of this technology, there are currently no data linking the de-inking efficiency with typical printing ink compositions. Additionally, it is necessary to investigate the de-inking process under the process parameters of existing recycling plants, including temperature, NaOH concentration, and retention time. This study aims to evaluate the performance of commonly used printing inks with different compositions under various washing scenarios for plastic recycling in conjunction with different de-inking detergents containing surfactants or mixtures of surfactants. The results indicate that the pigments applied to the ink have no significant effect on the de-inking process, except for carbon black (PBk 7). Nitrocellulose (NC) binder systems exhibit high de-inkability (over 95%) under the condition of 55 °C and 1 wt.% NaOH. However, crosslinked binder systems can impede the de-inking effect, whether used as a binder system or as an overprint varnish (OPV). The de-inking process requires heating to 55 °C with 1 wt.% NaOH to achieve a substantial effect. Based on the findings in this work, breaking the Van der Waals forces, hydrogen bonds, and covalent bonds between the printing ink and plastic film is an essential step to achieve the de-inking effect. Further research is needed to understand the interaction between surfactants and printing inks, enabling the development of de-inkable printing inks and high-performance surfactants that allow for de-inking with less energy consumption. The surfactant and NaOH have a synergistic effect in cleaning the printing ink. NaOH provides a negative surface charge for the adsorption of the cationic head of the surfactant and can hydrolyze the covalent bonds at higher concentrations (>2 wt.%).