Effect of erlotinib combined with cisplatin on tumor growth, interleukin-6 (IL-6) and interleukin-12 (IL-12) in mice with Lewis lung cancer (LLC) was investigated. Forty-four pure inbred SPF C57BL/6J mice were modeled for LLC and randomized into groups A, B, C and D (n=11 each group). Mice in group A were given normal saline, group B was given erlotinib, group C was given cisplatin injection and group D erlotinib combined with cisplatin. Tumor growth of the mice was observed and the tumor mass was measured. Serum IL-6 and IL-12 levels were measured by enzyme-linked immunosorbent assay (ELISA) 40 days later. At different time-points after medication, tumor volume in group D was significantly lower than that in groups A, B and C (P<0.05), and that in groups B and C was significantly lower than that in group A (P<0.05), whereas there was no significant difference between groups B and C (P>0.05). Tumor mass in groups B, C and D was significantly lower than that in group A (P<0.05), and that in group D was significantly lower than that in groups B and C (P<0.05), whereas there was no significant difference between groups B and C (P>0.05). Compared with groups B and C, mice in group D had significantly lower IL-6 level (P<0.05), but significantly higher IL-12 level (P<0.05). There was no significant difference in IL-6 and IL-12 levels between groups B and C (P>0.05). In conclusion, erlotinib combined with cisplatin can inhibit the tumor growth of mice with LLC, and inhibition of IL-6 level and upregulation of IL-12 level may be one of its therapeutic mechanisms. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License.