Background: Tumor hypoxia has been widely reported to promote metastasis. However, the molecular mechanisms underlying metastasis-associated hypoxia remain unclear. Formyl peptide receptor 1 (FPR1) has been reported to be highly expressed under hypoxic conditions. This study aimed to explore the role of FPRI in tumor cells under hypoxic conditions. Methods: The expressions of FPRI and hypoxia-inducible factor 1 alpha (HIF-1 alpha) in A549 cells under hypoxic conditions were detected using western blot. The expression of FPRI in A549 cells under hypoxic conditions was suppressed using the FPRI antagonist Boc2. Wound-healing and Transwell assays were performed to investigate the migration and invasion of cells. Furthermore, the tumorigenicity of A549 cells was evaluated by constructing a hypoxic mouse model of lung adenocarcinoma. The expression levels of HIF- 1 alpha and FPR1 in tumors were measured by real-time polymerase chain reaction (PCR) and western blot. Results: The expression levels of FPRI and HIF- 1 alpha increased in a time-dependent manner after exposure to hypoxic conditions. Wound-healing and Transwell assays showed that hypoxia promoted the migration and invasion abilities of A549 cells, whereas downregulation of FPRI blocked the effects of hypoxia on A549 cells. Our in vivo results demonstrated that the tumor volumes and weights of mice exposed to hypoxic conditions were significantly higher than those of untreated mice. Furthermore, the downregulation of FPRI blocked the effects of hypoxia in the mice. Meanwhile, the expressions of HIF-1 alpha and FPRI at the protein and mRNA levels were increased after hypoxic exposure, whereas FPRI antagonist Boc2 suppressed the effect of hypoxia on the expression of FPR1. Conclusions: Our results suggest that FPRI could be a therapeutic target for suppressing the invasion and tumorigenicity of lung adenocarcinoma cells.