As a kind of important innate lymphocytes in vivo, Natural killer (NK) cells have a rapid and efficient capacity to recognize and destroy tumor cells, senescent cells and virus-infected cells. In the past decades, NK cells have been widely applied in the treatment of hematological malignancies in clinic, even solid tumors. Successful results have been made against hematological malignancies (NCT00697671, NCT00990717, NCT00145626), but also a number of considerable challenges have been encountered during this period, such as poor outcomes in the treatment of solid tumors, difficult to migrate to and infiltrate into tumor sites, little functioning NK cell was seen in tumor stroma. Now we know tumor microenvironment has great influence on NK cell function, phenotype and activation, and it can finally give rise to NK cell dysfunction or/and exhaustion. Many strategies have been made to try to overcome those drawbacks. In this review, we discuss the current strategies to increase the NK cell-mediated tumor cell killing capacity and homing to the solid tumor site with the aim of heightening the clinical outcome in NK cell-based immunotherapy against solid cancer.