Background and Objectives: To report on the first results of safety, efficacy, and outcome of CT-navigated stereotactic percutaneous electrochemotherapy (SpECT) in patients with primary and secondary liver malignancies. Methods: This retrospective study included 23 consecutive lesions in 22 patients who underwent SpECT for primary and secondary malignant liver lesions with locally curative intention. The endpoints were primary technique efficacy (PTE), local tumor progression (LTP), time to progression (TTP), and occurrence of adverse events. Results: The mean maximum diameter of the treated lesions was 42 mm (range: 16 mm–72 mm). Eight lesions were hepatocellular carcinoma (34.8%), five lesions were colorectal liver metastases (21.7%), three lesions were cholangiocellular carcinoma (13.0%), and the other seven lesions were liver metastases from different primary cancers (30.4%). PTE was achieved for 22 lesions (95.7%). The mean follow-up time was 15 months (0–39 months). No LTP was observed. In six patients (27.3%), hepatic tumor progression was observed during follow-up with a mean TTP of 3.8 months (2–8 months). In 10 procedures (43.5%), minor complications (1 CIRSE Grade 2) and side effects occurred, but no major complications were observed. Conclusions: SpECT seems to be a safe and effective new local treatment modality for primary and secondary liver malignancies.