It’s hypothesized that LRRC8A may regulate cell proliferation and migration by participating in the transduction of cell signaling. Then protein phosphorylation in cells with or without the over-expressed LRRC8A was detected and quantified by mass spectroscopy. A total of 564 proteins and 1,102 phosphorylated sites were identified, of which 342 proteins and 538 phosphorylated sites were successfully quantified. A total of 32 downregulated and 68 upregulated proteins were noted in the OE-LRRC8A group compared with the LV-ctrl group; the intensities of 79 phosphorylated sites in 62 proteins were considerably altered by the overexpression of the LRRC8A protein; all the differential sites included 41 downregulated sites and 38 upregulated sites.