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We developed anin silicoapproach to model B16F10 melanoma cell response to a helium atmospheric pressure plasma jet (APPJ) or/and doxorubicin drug (DOX). Thein silicomodel is informed by relevant data from previously publishedin vitroexperiments (cancer cell viability), providing detailed information on (i) cell population number (Ncell) development during incubation and (ii) probability values for apoptosis (%PApoptosis) and mitosis (%PMitosis) following cell subjection to the plasma-conditioned RPMI-1640 medium (PC-RPMI), DOX, and DOX combined with APPJ. When treating cancer cells with PC-RPMI and DOX separately, at the smallest plasma duration (dPlasma = 15 s) and DOX concentration (cDOX = 0.05 μM), only a small decline in Ncell, an increase in %PApoptosis, or/and a decrease in %PMitosisare measured with respect to the control conditions (non-treated cancer cells). However, cell cytotoxicity is increasingly enhanced with increasingdPlasmaandcDOXup to 120 s and 0.5 μM, respectively. At those highest values studied inin silico, simulated %PApoptosisare significantly larger than %PMitosis, resulting in a severe decrease in Ncellcompared to control in agreement with the correspondingin vitroexperiments.&nbsp