Objective To investigate the mechanism of HIP68/RAP1B signaling pathway on breast cancer invasion and metastasis. Methods A total of 73 breast cancer tissue samples were selected from the First Affiliated Hospital of Xi 'an Jiaotong University during 2012-2013. Immunohistochemical samples and clinical data were used to analyze the expression of HIP68/RAP1B and its relationship with pathological features. Anoxic breast cancer cells were constructed from breast cancer cell lines MCF-7 and MDA-MB-231 in vitro. The expression of HIP68/RAP1B was determined in hypoxic breast cancer cell lines (MCF-7 and MDA-MB-231) and normal breast epithelial cell lines SK-BR-3, respectively. Breast cancer cells with high/low expression of HIP68 were constructed to observe their effects on RAP1B protein and biological behavior of breast cancer cells. Breast cancer cells with silenced/overexpression of RAP1B were silenced to observe their effects on HIP68 protein and biological behavior of breast cancer cells. The binding site of HIP68/RAP1B was detected by co-immunoprecipitation. Results The expressions of HIP68 and RAP1B proteins in breast cancer tissues were higher than those in paracancer tissues (P<0.05). The expression of HIP68 was correlated with TNM stage and lymph node metastasis (P<0.05). RAP1B was correlated with TNM stage, lymph node metastasis, ER and RR status (P<0.05). There was a positive correlation between HIP68 expression and RAP1B expression (r=0.427, P<0.05). HIP68/RAP1B was highly expressed in hypoxic breast cancer cells. The expression of RAP1B protein was positively correlated with HIP68 expression, and high expression of HIP68/RAP1B promoted cell invasion and metastasis, while low expression of HIP68/RAP1B inhibited cell invasion and metastasis. IP68 protein did not change due to the high/low expression of RAP1B protein, but the high expression of RAP1B protein promoted the proliferation, invasion and metastasis of breast cancer cells. The results of co-immunoprecipitation showed that RAP1B may be the downstream of HIP68 gene. Conclusion The HIP68/RAP1B signaling pathway is highly expressed in breast cancer tissues and promotes breast cancer cell migration and invasion