Serine protease inhibitor Kazal type 1 (SPINK1) plays a role in protecting the pancreas against premature activation of trypsinogen and is involved in cancer progression. SPINK1 promoted LAC cells growth, migration and invasion. Mechanistically, we found that SPINK1 promoted LAC cells migration and invasion via up-regulating matrix metalloproteinase 12 (MMP12). We observed that SPINK1 expression was only up-regulated in lung adenocarcinoma (LAC) tissues, and was an independent prognostic factor for poor survival.Our results indicate that SPINK1 might be a potential biomarker for LAC that promotes progression by MMP12.