The program of potato protection recommended by the producers of agrochemicals requires application: thiamethoxam, lambda-cyhalothrin, deltamethrin, rimsulfuron and metalaxyl. Therefore, there is a risk that these pesticides are present in tubers, thus posing a toxicological risk to the consumer. In this respect, it is necessary to monitor the presence of these compounds in edible plants. Therefore, the aim of this paper was to develop a novel, simple and robust analytical procedure for simultaneous determination of above-mentioned pesticides in potato tubers. To develop an analytical procedure that fulfills SANTE demands, quick, easy, cheap, effective, rugged and safe method and matrix solid phase dispersion technique were investigated. The final determination was conducted by liquid chromatography with tandem mass spectrometry. The obtained experimental data were analyzed by analysis of variance. For the extraction of analytes, matrix solid phase dispersion with octadecyl sorbent and methanol as eluent was chosen, since it provides the validation parameters according to SANTE requirements (recovery: 77-111%, relative standard deviation: 1-10%, limit of quantification: 0.9-5.0μg/kg). This innovative analytical procedure is a practical analytical tool, which was successfully proven by applying it for target pesticides determination in potato tuber samples of different varieties randomly chosen at local markets.