Abstract. 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.