Treatment of either OMM2.5 (GNAQQ209P) or OMM1 (GNA11Q209L) uveal melanoma cells with T/CQ resulted in increased cell death compared with vehicle or single agents. In addition, similar observations were made using Melan-a/GNAQQ209L or Melan-a/GNA11Q209L cells...the antiproliferative effects of T/CQ treatment were calculated to be synergistic in all four cell lines...These results demonstrated that T/CQ is effective in eliciting synergistic cytotoxicity in GNAQ/11-mutated melanoma cell lines in vitro. Hence, using four different models of GNAQ- or GNA11-driven melanoma, we demonstrate that T/HCQ combination inhibits melanoma growth, either subcutaneous or in the liver, with or without the presence of an intact immune system, and also provides a survival advantage to T/HCQ-treated tumor-bearing mice.