Background: The celiac plexus and splanchnic nerves are targets for neurolytic blocks for pain relief from pain caused by upper gastrointestinal tumors. Therefore, we investigated the analgesic effect of a celiac plexus block versus a splanchnic nerve block and the effects of these blocks on the quality of life six months post-intervention for patients with upper GIT tumors. Methods: Seventy-nine patients with inoperable upper GIT tumors and with severe uncontrolled visceral pain were randomized into two groups. These were Group I, for whom a celiac plexus block was used with a bilateral needle retrocrural technique, and Group II, for whom a splanchnic nerve block with a bilateral needle technique was used. The visual analogue scale for pain (0 to 100), the quality of life via the QLQ-C30 questionnaire, and survival rates were assessed. Results: Pain scores were comparable in both groups in the first week after the block. Significantly more patients retained good analgesia with tramadol in the splanchnic group from 16 weeks onwards (P = 0.005, 0.001, 0.005, 0.001, 0.01). Social and cognitive scales improved significantly from the second week onwards in the splanchnic group. Survival of both groups was comparable. Conclusions: The results of this study demonstrate that the efficacy of the splanchnic nerve block technique appears to be clinically comparable to a celiac block. All statistically significant differences are of little clinical value.