Background: Advanced melanoma with liver metastasis has reduced response to anti-PD-1 monotherapy with ORR of 4.3% in a pooled analysis, and initial results of the phase 1b trial, systemic toripalimab combined with intrahepatic OrienX010 injection - a HSV-1-derived oncolytic virotherapy with expression of GM-CSF had shown its efficacy. Here we report the RFS and OS outcomes. Methods: Eligible pts included those over 18 with injectable liver metastasis confirmed by biopsy with or without extra-hepatic metastasis; the ocular melanoma and brain metastasis were excluded. Pts received intravenous toripalimab Q2W combined with ultrasound guided intratumoral injection of OrienX010 Q2W (8×10⁷ pfu/ml, 10ml per injection) until intolerance or disease progression per iRECIST criteria. Liver biopsy would be performed at baseline and first tumor evaluation (8-12weeks). The primary endpoint was toxicity; secondary endpoints included ORR, DCR and PFS. Results: From Jul 2019 to Jan 2022, 23 pts were eligible and enrolled. Baseline characteristics: median age 69 yrs; primary: mucosal 60.9%, cutaneous 13.0%, unknown primary 13.0%, acral 13.0%; gene mutation status: Braf 17.4%, Nras 4.3%; 69.6% got extra-hepatic metastasis: regional or distant lymph node 56.3%, lung 37.5%, bone 31.3%; LDH＞ULN 26.1%; median size of injected lesions: 35mm(10-94mm); median number of liver metastasis: 7(1-10); median number of injection: 10 (3-36). Among these pts, 20 pts could be evaluated for efficacy. The median PFS was 7.0 months (95%CI: 4.3-9.7 months) and the median OS was 18.6 months (95%CI: 13.4-23.7 months) with a median follow-up time of 19.8 months (range, 0.9-29.7). The global ORR by investigator was 15% (3/20), DCR 50% (10/20); the response rate was 35%(7/20) for injected lesions, 27.8%(5/18) for non-injected lesions in liver, and 26.7% (4/15) for extra-hepatic metastases. Biopsies of 15 pts for injected lesions at 8 to 12 weeks after first injection were examined to determine the situation of TIL infiltration. Among them, the median PFS of the pts (7/15) with impressive TIL infiltration (Brisk n = 4 and Nonbrisk n = 3 according to the definition of AJCC 8th edition) was 7.8 months (95%CI: 2.8-12.8 months) versus 4.1 months (95%CI: 0-9.1 months) of the pts without impressive TIL infiltration. For pts（21.7%( 2 PR and 3 SD)）with no melanoma cells residual by immunohistochemistry in biopsies the median PFS was 13.8 months (95%CI: 4.0-23.6 months), and it was much longer than that of other pts which was 5.6 months (95%CI: 2.4-8.8 months). The median OS of the pts with no melanoma cells was 19.7 months (95%CI: 7.5-31.9 months). Conclusions: Systemic toripalimab combined with intrahepatic OrienX010 injection has shown remarkable long PFS and OS in melanoma pts with liver metastases. Clinical trial information: NCT04206358.